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THE 

ELEMENTS  OF  THE  SCIENCE 

OF 


NUTRITION 


BY 


PROFESSOR 

./-u  ju-uvi    i_,\^kji-s.,  1  n.  Ly.,  lJv„.  l^.,  i  .i\.o.   v^-'L-'iin.; 

OF    PHYSlC>LOGY    AT    THE    CORNELL    UNIVERSITY    MEDICAL    COLLEGE, 
NEW    YORK    CITY 

SECOND  EDITION.  REVISED  AND 

ENLARGED 

PHILADELPHIA   AND   LONDON 

w. 

B.     SAUNDERS    (COMPANY 

1909 

Set  up,  electrotyped,  printed  and  copyrighted  September.,  1906.     Revised, 
entirely  reset,  reprinted  and  recopyrighted,  November,  1909. 


Copyright,  1909,  by  W.  B.  Saunders  Company. 


PRINTED    IN    AMERICA 

PRESS    OF 

W.    B.    SAUNDERS    COMPANY 

PHILADELPHIA 


To  THE  Memory  of 
CARL  VON  VOIT 

MASTER    AND    FRIEND 

FROM    WHOM    THE    AUTHOR    RECEIVED    THE     INSPIRATION 

OF    HIS    life's    WORK 

THIS    VOLUME    IS    DEDICATED. 


"  The  greatest  joy  of  those  who  are  steeped  in  work  and  who 
have  succeeded  in  finding  new  truths  and  in  understanding  the 
relations  of  things  to  each  other,  lies  in  work  itself." 

Carl  von  VoiL 


PREFACE  TO  THE  SECOND  EDITION. 


This,  the  second  edition  diiTers  chiefly  from  its  predecessor  in 
containing  facts  which  have  been  brought  to  light  during  the 
past  three  years. 

The  aim.  of  the  book  is  to  review  the  scientific  substratum 
upon  which  rests  the  knowledge  of  nutrition  both  in  health 
and  in  disease.  Throughout,  no  statement  has  been  made 
^\•ithout  endeavoring  to  give  the  proof  that  it  is  true. 

The  widespread  interest  in  the  subject  of  nutrition  at  the 
present  time  leads  the  author  to  hope  that  this  book  may  prove 
of  value  to  the  student  of  dietetics  and  to  the  clinical  physician. 

Laboratory  methods  to  explain  the  inner  processes  in  dis- 
ease have  been  applied  to  hospital  patients  for  twenty  years 
or  more  in  Germany,  but  in  the  United  States  little  has  been 
done  in  this  regard.  If  such  investigations  are  in  any  way 
promoted  by  their  discussion  here,  this  wiriting  will  not  have 
been  in  vain. 

On  a  previous  occasion  the  author  collected  the  more  im- 
portant information  concerning  the  life  history  of  the  mineral 
constituents  of  the  body  for  the  American  Text  Book  of  Physi- 
ology, and  the  subject  has  been  allotted  but  little  space  in  this 
volume. 

The  author  would  apologize  to  all  whose  claims  of  priority 
of  discovery  have  not  been  duly  recognized. 

He  wishes  to  express  his  great  obligation  to  a  former  pupil. 
Dr.  Margaret  B.  Wilson,  who  has  painstakingly  corrected  the 
manuscript  and  proof.  He  gratefully  acknowledges  the  kind 
encouragement  of  his  former  colleagues  at  the  University  and 
Bellevue  Hospital  Medical  College  and  the  helpful  criticism  of 
many  friends. 

Graham  Lusk. 

Physiological  Laboratory,  Cornell 

University  Medical  College, 

New  York,  November,  1909. 

13 


CONTENTS. 


CHAPTER  I.  Page. 

Introductory 17 

CHAPTER  II. 
Starvation 54 

CHAPTER  III. 
The  Regulation  of  Temperature 86 

CHAPTER  IV. 
The  Influence  of  Protein  Food — Part  1 107 

CHAPTER  V. 
The  Influence  of  Protein  Food — Part  II 128 

CHAPTER  VI. 
The  Specific  Dyn.amic  Action  of  the  Foodstuffs 156 

CIL\PTER  VII. 
The  Influence  of  the  Ingestion  of  Fat  and  Carbohydrate 165 

CHAPTER  VIII. 
The  Influence  of  Mech.anical  Work  on  Metabolism 190 

CHAPTER  IX. 
A  Normal  Diet : 210 

CHAPTER  X. 
The  Food  Requirement  During  the  Period  of  Growth 228 

CHAPTER  XL 
Metabolism  in  Anemia,  at  High  Altitudes,  in  Myxedema  and  in 
Exophthalmic  Goiter 253 

CHAPTER  XII. 
Metabolism  in  Diabetes  and  in  Phosphorus-Poisoning 271 

CHAPTER  XIII. 
Metabolism  in  Fever 311 

CHAPTER  XIV. 
PuRiN  Metabolism. — Gout 335 

CHAPTER  XV. 
Theory  of  Metabolism 357 


Appendix 363 

Index  of  Authors 375 

Index  of  Subtfxts 387 


THE  ELEMENTS  OF  THE   SCIENCE 
OF  NUTRITION. 


CHAPTER  I. 
INTRODUCTORY. 

The  earliest  scientific  observations  concerning  nutrition  were 
founded  upon  the  commonly  noted  fact  that  in  spite  of  the 
ingestion  of  large  quantities  of  food,  a  normal  man  did  not  vary 
greatly  in  size  from  year  to  year.  It  was  understood  early  in 
the  history  of  physiology  that  the  weight  added  by  the  ingestion 
of  food  and  drink  was  lost  in  the  urine,  the  feces,  and  the  "in- 
sensible perspiration."  The  "insensible perspiration "  was  partly 
in  evidence  when  moisture  of  the  warm  breath  condensed  upon 
a  cold  plate.  By  it  were  meant  the  usually  invisible  exhalations 
from  the  body,  which  are  now  known  to  be  carbon  dioxid  and 
water. 

Sanctorius^  made  many  experiments  upon  himself  and  others 
to  determine  the  amount  of  insensible  perspiration.  An  old 
cut  shows  him  sitting  in  a  chair  suspended  from  a  large  steel- 
yard. As  a  matter  of  routine  he  determined  his  own  weight 
previous  to  each  meal  and  then  weighted  the  steelyard  so  as  to 
counterbalance  the  additional  food  he  proposed  to  eat.  During 
the  meal  when  the  chair  dipped  he  ended  his  repast. 

In  Section  I,  Aphorism  II,  Sanctorius  gives  the  following 
curious  advice:  "If  a  physician  who  has  the  care  of  another's 
health,  is  acquainted  only  with  the  sensible  supplies  and  evacua- 
tions, and  knows  nothing  of  the  waste  that  is  daily  made  by  the 
insensible  perspiration,  he  will  only  deceive  his  patient  and  never 
cure  him."     Aphorism  III  reads:    "He  only  who  knows  how 

'Sanctorius:     "De   medicina  statica  aphorismi,"   Venice,    1614.     Trans- 
lation by  John  Quincy,  M.D.,  London,  1737. 
2  17 


l8  SCIENCE   OF   NUTRITION. 

much  and  when  the  body  does  more  or  less  insensibly  perspire, 
will  be  able  to  discern  when  or  what  is  to  be  added  or  taken 
away  either  for  the  recovery  or  preservation  of  health." 

In  1668  John  Mayow,  writing  in  London,  stated  that  the 
atmosphere  contained  a  constituent  which  supported  combus- 
tion as  well  as  animal  life. 

The  modern  era  of  the  science  of  nutrition  was  opened  by 
Lavoisier.  The  work  of  to-day  is  but  the  continuation  of  that 
done  a  century  and  more  ago.  Lavoisier  and  La  Place  made  ex- 
periments on  animal  heat  and  respiration.  The  great  German 
chemist  Liebig  received  his  early  training  in  Paris,  residing  there 
in  1822.  Liebig's  conception  of  the  processes  of  nutrition  fired 
the  genius  of  Voit  to  the  painstaking  researches  which  laid  the 
foundation  of  his  Munich  school.  These  have  been  repeated 
and  extended  by  his  pupils,  of  whom  Rubner  is  chief,  and  by 
others  the  world  over.  Thus  the  knowledge  often  transmitted 
personally  from  the  master  to  the  pupil,  to  be  in  turn  elaborated, 
had  its  seed  in  the  intellect  of  Lavoisier.  It  was  he  who  first 
discovered  the  true  importance  of  oxygen  gas,  to  which  he  gave 
its  present  name.  He  declared  that  life  processes  were  those  of 
oxidation,  with  the  resulting  elimination  of  heat.  He  believed 
that  oxygen  was  the  cause  of  the  decomposition  of  a  fluid  brought 
to  the  lungs,  and  that  hydrogen  and  carbon  were  produced  in 
this  fluid  and  then  united  with  oxygen  to  form  water  and  carbon 
dioxid.  It  was  he  who  first  made  respiration  experiments  on 
man,  the  results  of  which  are  briefly  described  in  a  letter  to 
Monsieur  Terray,^  written  in  Paris  and  dated  November  19, 
1790.  There  is  no  existing  record  of  the  apparatus  with  which 
Lavoisier  worked  and  early  obtained  accurate  results.  The 
more  important  conclusions  Lavoisier  sums  up  as  follows: 

I.  The  quantity  of  oxygen  absorbed  by  a  resting  man  at  a 
temperature  of  26°  C.  is  1200  pouces  de  France^  hourly. 

^Report  of  the  British  Association  for  the  Advancement  of  Science,  Edin- 
burgh, 1871,  p.  189. 

^  I  cubic  pouce  =  0.0198  liters. 


INTRODUCTORY.  1 9 

2.  The  quantity  of  oxygen  required  at  a  temperature  of  12°  C. 

rises  to  1400  ponces. 

3.  During  the  digestion  of  food    the   quantity  of  oxygen 

amounts  to  from  1800  to  igoo  ponces. 

4.  During  exercise  4000  pouces  and  over  may  be  the  quantity 

of  oxygen  absorbed. 

These  remarkable  results  are  in  strict  accord  with  the 
knowledge  of  our  own  day.  We  know  more  details,  but  the 
fundamental  fact  that  the  quantity  of  oxygen  absorbed  and  of 
carbon  dioxid  excreted  depends  primarily  on  (i)  food,  (2)  work, 
and  (3)  temperature,  was  established  by  Lavoisier  within  a  few 
years  after  his  discovery  that  oxygen  supported  combustion. 

It  was,  however,  quickly  noted  that  if  carbon  and  hydrogen 
burned  in  the  lungs,  the  greatest  heat  would  be  developed  there, 
a  result  not  in  accordance  with  observation.  It  was  then  sug- 
gested that  the  blood  dissolved  oxygen,  and  that  the  production 
of  carbon  dioxid  and  water  took  place  through  oxidation  within 
the  blood.  In  1837  Magnus  discovered  that  the  blood  did  hold 
large  quantities  of  oxygen  and  carbon  dioxid,  which  gave  appar- 
ent support  to  this  theory.  Ludwig  in  his  later  years  believed 
that  the  oxidation  took  place  in  the  blood. ^  Through  the  criti- 
cal studies  of  Liebig,  which  were  published  in  1842,  it  was  seen 
that  it  was  not  carbon  and  hydrogen  which  burned  in  the  body, 
but  protein,  carbohydrates,  and  fat.  Liebig's  original  theory 
was  that  while  oxygen  caused  the  combustion  of  fat  and  carbo- 
hydrates, the  breaking  down  of  protein  was  caused  by  muscle 
work.  It  will  be  shown  later  that  oxygen  is  not  the  cause  of  the 
decomposition  of  materials  in  the  body,  but  that  this  decomposi- 
tion proceeds  from  unknown  causes,  and  the  products  involved 
unite  with  oxygen.  The  sum  of  these  chemical  changes  of  mate- 
rials under  the  influence  of  living  cells  is  known  as  metabolism. 
This  process  may  involve  two  factors,  catabolism,  or  the  reduction 
of  higher  chemical  compounds  into  lower,  and  anaholism,  or  the 
construction  of  higher  substances  from  lower  ones. 

'  Oral  statement  to  the  writer. 


20  SCIENCE    OF   NUTRITION. 

Liebig  was  also  the  father  of  the  modern  methods  of  organic 
analysis,  and  with  him  began  the  great  accumulation  of  knowl- 
edge concerning  the  chemistry  of  the  carbon  compounds,  includ- 
ing many  products  of  the  animal  economy.  These  discoveries 
gave  the  world  a  knowledge  of  the  constitution  of  foods,  of  urine, 
of  feces,  and  of  tissues,  which  was  not  possessed  by  Lavoisier. 

Liebig  applied  to  the  problems  of  biology  the  mental  wealth 
of  the  newer  chemistry  which  he  himself  was  creating.  He 
knew  that  protein  contained  nitrogen,  and  in  1842  he  suggested 
that  the  nitrogen  in  the  urine  might  be  made  a  measure  of  the 
protein  destruction  in  the  body.^  Bidder  and  Schmidt^  were 
the  first  to  make  systematic  experiments  upon  this  subject. 
They  gave  meat  to  dogs  and  cats  and  found  that  almost  all  the 
nitrogen  contained  in  the  meat  was  eliminated  in  the  urine  and 
in  the  feces.  They^  make  the  following  striking  statement, 
which  rings  quite  true  to  modern  thought,  concerning  protein 
metabolism:  "Almost  all  the  nitrogen  of  protein  and  collagen 
is  split  from  its  combination  and  carries  with  it  enough  carbon, 
hydrogen  and  oxygen  to  form  urea;  the  remaining  part,  con- 
taining five-sixths  of  the  total  heat  value  of  the  protein,  under- 
goes oxidation  to  carbon  dioxid  and  water  which  are  eliminated 
in  the  respiration,  the  calorifacient  function  having  been  ful- 
filled." The  results  obtained  by  Bidder  and  Schmidt  were 
attacked  and  were  not  finally  established  until  proof  was  afforded 
by  Carl  v.  Voit,*  who  established  the  fact  that  an  animal  could 
be  brought  into  what  he  called  nitrogenous  equilibrium.  In  this 
condition  the  nitrogen  of  the  protein  eaten  was  equal  to  the 
nitrogen  efiminated  from  the  body  in  the  urine  and  feces.  Thus 
Voit^  fed  a  dog  for  fifty-eight  days  with  29  kilograms  of  meat 

^Liebig:  "Die  organische  Chemie  in  ihrer  Anwendung  auf  •  Physiologie 
und  Pathologic,"  1842. 

^Bidder  and  Schmidt:  "Die  Verdauungssafte  und  der  Stoffwechsel," 
1852,  pp.  333  and  339. 

^Bidder  and  Schmidt:   Loc.  cit.,  p.  387. 

*Voit:   "Physiol.  Chem.  Untersuchungen,"  1857. 

^Voit:   "Zeitschrift  fur  Biologie,"  1866,  Bd.  ii,  p.  35. 


INTRODUCTORY.  21 

containing  986.0  grams  of  nitrogen,  and  found  982.8  grams  of 
nitrogen  in  the  excreta  of  the  period.  The  amount  of  N  in 
the  urine  was  943.7  grams,  and  in  the  feces  39.1  grams.  The 
difference  between  the  amount  of  nitrogen  ingested  and  that  re- 
covered in  the  excreta  was  only  three-tenths  of  one  per  cent. 
It  therefore  seemed  extremely  probable  that  the  excretory  outlet 
for  protein  nitrogen  was  in  the  urine  and  in  the  feces  and  that 
other  sources  of  its  loss  were  normally  negligible.  But  in  order 
to  establish  the  fact  it  was  necessary  to  consider  the  following 
questions : 

Is  the  nitrogen  of  the  air  built  up  into  organic  compounds 
within  the  body  ?  Is  any  protein  nitrogen  given  off  as  nitrogen 
gas?  As  ammonia  gas?  In  the  sweat?  How  much  is  lost 
through  the  growth  of  the  hair,  nails,  and  epidermis? 

Lavoisier  had  said  that  nitrogen  gas  had  nothing  to  do  with 
respiration.  Regnault  and  Reiset^  sometimes  found  that  ani- 
mals under  a  bell-jar  absorbed  nitrogen  gas  and  at  other  times 
gave  it  off.  The  quantity  in  both  cases  was  extremely  small. 
Voit  explained  this  by  showing  that  the  blood  and  the  tissues 
always  contained  nitrogen  gas  dissolved  in  proportion  to  the 
partial  pressure  of  the  gas  in  the  atmosphere.  A  change  of  this 
partial  pressure  under  the  bell-jar  would  change  the  body's 
content  of  dissolved  nitrogen  and  explain  Regnault  and  Reiset's 
variations. 

The  experiments  of  BachP  showed  that  a  rabbit  with  a 
tracheal  cannula  could  be  made  to  expire  for  six  hours  through 
Nessler's  reagent  without  the  indication  of  a  trace  of  ammonia 
in  the  breath.  This  has  also  been  shown  after  making  an 
Eck  fistula  in  a  dog,^  where  there  is  an  increase  in  the  amount 
of  ammonia  in  the  blood  and  in  the  urine.  The  lungs  are  not 
permeable  to  ammonia.'*     The  ordinary  insensible  perspiration 

'  Regnault  and  Rciset:  "An.  de  chimic  et  phys.,"  Paris,  1849,  Sec.  3,  Tome 
x.wi. 

*Bachl:   "Zeitschrift  fur  Biologic,"  1869,  Bd.  v,  p.  61. 

*Salaskin:   "Zeitschrift  fiir  physiologische  Chemie,"  1898,  Bd.  xxv,  p.  463. 
*  Magnus:    "Archiv  fiir  ex.   Pathologic   und   Pharmakologie,"    1902,   Bd. 
xlviii,  p.  100. 


22  SCIENCE    OF   NUTRITION. 

is  not  accompanied  by  any  appreciable  loss  of  nitrogenous 
excreta,  although  profuse  sweating  certainly  brings  out  some 
urea,  uric  acid,  and  other  nitrogen  extractives  normally  excreted 
in  the  urine.  The  recent  experiments  of  Benedict^  show  that 
the  cutaneous  excretions  of  a  resting  man  may  amount  to  0.071 
gram  nitrogen  per  day;  of  a  man  at  moderate  work  to  0.13 
gram  per  hour,  and  at  hard  work  for  four  hours  to  0.22  gram 
per  hour. 

Voit^  collected  the  hair  and  epidermis  from  a  dog  for  565 
days  and  found  an  average  daily  output  of  1.2  grams  with  0.18 
gram  of  nitrogen.  Moleschott^  cut  the  hair  and  nails  of  several 
men  once  a  month.  The  daily  outgrowth  of  hair  was  0.20  gram 
with  0.029  gram  of  nitrogen,  and  of  nail  substance  0.005  gram 
with  0.0007  gram  of  nitrogen.  The  waste  through  the  human 
epidermis  has  not  been  measured,  but  it  must  be  very  slight. 
The  above  sources  of  error  were  thus  shown  to  be  negligible. 

The  view  that  the  nitrogen  of  the  urine  and  feces  could  be 
made  a  measure  for  the  determination  of  protein  metabolism 
was  thus  securely  established.  Urea,  the  principal  nitrogenous 
end-product  derived  from  protein,  was  therefore  shown  to  be 
not  an  adventitious  product,  but  one  normally  proportional  to 
the  protein  destruction.  It  was  known  that  meat  protein  in 
general  contained  about  16  per  cent,  of  nitrogen,  or  i  gram  of 
nitrogen  in  6.25  grams  of  protein.  Therefore  for  every  gram  of 
nitrogen  found  in  the  excreta,  6.25  grams  of  protein  have  been 
destroyed  in  the  body.  It  is  evident  that  if  protein  nitrogen 
be  retained  in  the  body  a  new  construction  of  body  tissue  is 
indicated,  whereas  if  more  nitrogen  is  eliminated  than  is  in- 
gested with  the  food,  a  waste  of  body  tissue  must  take  place. 
The  discovery  of  the  method  of  calculating  the  protein  metab- 
olism led  Voit  to  suggest  to  Pettenkofer  that  he  construct  an 
apparatus  with   which   the   total  carbon  excretion  might  be 

^Benedict:   "Journal  of  Biological  Chemistry,"  1906,  vol.  i,  p.  263. 
^  Voit:   "Zeitschrift  fiir  Biologic,"  1866,  Bd.  ii,  p.  207. 
^Moleschott:   " Untersuchungen  zur  Naturlehre,"  Bd.  xii,  p.  187. 


INTRODUCTORY.  23 

measured,  including  that  of  the  respiration  as  well  as  that  of  the 
urine  and  the  feces.  Voit  saw  that  with  these  data  it  would  be 
possible  to  determine  just  how  much  of  each  foodstuff  was 
actually  burned  in  the  human  body.  He  has  described  the 
delight  which  he  and  Pettenkofer  experienced  when  their  won- 
derful machine  began  to  tell  its  tale  of  the  life  processes.  The 
cost  of  the  apparatus,  which  was  considerable,  was  defrayed  by 
King  Maximilian  II  of  Bavaria. 

It  has  been  stated  that  the  form  of  Lavoisier's  respiration 
apparatus  is  unkno^^^l.  In  1850  Regnault  and  Reiset^  pub- 
lished an  account  of  respiration  experiments  in  which  small 
animals  were  placed  under  a  bell-jar  containing  a  known  quan- 
tity of  oxygen.  The  air  was  kept  free  from  carbon  dioxid  by 
pumping  it  through  potassium  hydrate.  The  gaseous  exchange 
between  the  animal  and  its  environment  could  be  readily  ascer- 
tained, by  determining  the  amount  of  carbon  dioxid  given  off 
and  the  amount  of  oxygen  absorbed.  No  attempt  was  made  to 
determine  from  what  materials  the  carbonic  acid  arose.  The 
method  of  Regnault  and  Reiset  placed  the  animals  in  a  confined 
space  where  poisonous  exhalations  other  than  carbon  dioxid 
could  collect,  and  where  the  atmosphere  became  saturated  with 
water.  Although  Regnault  and  Reiset  had  no  idea  of  the 
materials  which  were  oxidized  in  the  animals  with  which  they 
were  experimenting,  we  find  that  Bischoff  and  Voit^  tried  to  read 
such  interpretations  into  the  work  of  Regnault  and  Reiset.  Thus 
Bischoff  and  Voit  determined  the  quantity  of  nitrogen  in  the 
urine  of  a  starving  dog,  which  indicated  that  he  had  burned  in 
twenty-four  hours  218  grams  of  his  own  "flesh."  The  flesh 
was  calculated  from  the  nitrogen  elimination  on  the  basis  of 
the  knowledge  that  fresh  meat  contains  3.4  per  cent,  of  nitrogen. 
Many  of  the  older  experiments  were  computed  on  this  basis. 
It  was  shown  that  the  218  grams  of  "flesh"  contained  40  grams 

'Regnault  and  Reiset:  "An.  d.  Chem.  und  Pharm.,"  1850,  Bd.  Ixxiii, 
pp.  92,  129,  257. 

'Bischoff  and  Voit:  "Die  Gcsetze  dor  Krnalirung  des  Fleischfrcsscrs," 
i860,  p.  43. 


24  SCIENCE    OF   NUTRITION. 

of  carbon.  Bischoff  and  Voit  draw  attention  to  an  experiment 
of  Regnault  and  Reiset,  showing  that  a  meat-fed  dog  of  a  weight 
similar  to  the  above  gives  off  250  grams  of  carbon  and  absorbs 
900  grams  of  oxygen  in  the  respiration  of  twenty-four  hours. 
These  figures  indicated  to  Bischoff  and  Voit  that  the  extra 
carbon  ehmination  was  due  to  the  combustion  of  fat,  and  they 
reached  the  conclusion  that  the  waste  of  the  body  in  starvation 
is  dependent  on  the  metabolism  of  protein  and  fat.  Correct 
results,  however,  were  attainable  only  by  combining  the  two 
methods,  so  that  both  the  quantity  of  the  nitrogen  and  carbon 
of  the  urine  and  feces,  and  the  amount  of  carbon  dioxid  of  the 
respiration  during  the  same  period  of  time  could  be  ascertained. 
This  was  accomplished  by  the  respiration  apparatus  of  Petten- 
kofer. 

The  problem  to  be  solved  by  Pettenkofer  included  the  main- 
tenance of  a  man  in  normal  surroundings.  A  small  room  was 
therefore  constructed  which  was  well  ventilated  by  a  current  of 
air.  This  air  entered  the  chamber  freely  through  an  opening 
in  connection  with  a  large  room  outside  and  was  aspirated  from 
a  second  opening  in  the  chamber,  through  a  large  gas-meter, 
where  its  volume  was  measured  (500,000  liters  per  day).  It 
was  evidently  impracticable  to  determine  all  the  carbon  dioxid  in 
this  large  volume  of  air,  but  its  amount  was  calculated  from  the 
analysis  of  duplicate  samples  continually  withdrawn  from  the  air 
leaving  the  chamber  during  the  time  of  the  experiment.  Each 
sample,  as  it  was  pumped  out,  was  made  to  pass  over  calcined 
pumice  stone,  soaked  in  sulphuric  acid,  to  remove  the  water. 
Next  it  bubbled  through  baryta  water  to  remove  the  carbon 
dioxid,  and  then  passed  through  a  small  gas-meter,  where  the 
volume  of  the  sample  was  measured.  After  this  fashion  the 
amount  of  carbon  dioxid  and  water  coming  from  the  air  of  the 
chamber  was  determined  in  duplicate.  Other  duplicate  analyses 
of  the  air  taken  outside  the  ventilator,  just  before  it  entered  the 
chamber,  were  simultaneously  made  in  the  same  manner  as 
were  the  analyses  of  the  chamber  air  itself.  Knowing  the  quan- 
tity of  carbon  dioxid  and  water  entering  and  leaving  the  room, 


INTRODUCTORY.  25 

it  was  easy  to  calculate  how  much  was  derived  from  the  man 
li\'ing  in  it  during  the  period  of  experimentation.  The  experi- 
menters failed  to  find  any  other  gaseous  exhalation  from  a  man, 
such  as  ammonia,  hydrogen,  or  methane,  which  could  vitiate 
their  results.  Control  experiments  were  made  by  burning  a 
candle  or  evaporating  a  known  weight  of  water  within  the  room. 
Analysis  showed  that  the  carbon  dioxid  and  water  so  produced 
were  measurable  within  one  per  cent,  of  error. 

As  an  illustration  of  the  practical  working  of  the  respiration 
apparatus  the  first  experiment  of  Pettenkofer  and  Voit,^  which 
gives  the  metabolism  in  a  starving  man,  will  be  described.  The 
man  was  allowed  a  small  quantity  of  Liebig's  extract  of  beef, 
as  the  experimenters  did  not  at  that  time  realize  the  very  slight 
discomfort  usually  entailed  by  total  abstinence  from  food.  As 
Liebig's  extract  has  no  nutritive  value,  its  effect  has  been  counted 
out  in  the  following  description. 

The  subject,  on  entering  the  living-room  of  the  apparatus, 
weighed  71.090  kilograms,  and  he  drank  during  the  day  1.0548 
liters  of  water,  making  a  total  body  weight  of  72.1448  kilograms. 
Twenty-four  hours  later  he  weighed  70.160  kilograms  and  his 
excreta  had  amounted  to  0.7383  kilogram  carbon  dioxid,  0.8289 
kilogram  water  from  lungs  and  skin  and  1-1975  kilograms  of 
urine.  The  final  body  weight  plus  all  the  excreta  amounted  to 
72.9247  kilograms.  A  total  body  weight  of  72.1448  kilograms 
was  converted  into  a  body  weight  plus  excreta  amounting  to 
72.9247.  The  difference  is  due  to  oxygen  absorbed.  The 
difference  of  0.7799  kilogram  represents  the  amount  of  oxygen 
needed  to  convert  the  body  substance  lost  into  the  excretory 
products  obtained.     The  tabular  statement  reads : 

MAN— STARVATION. 

Kg.  Kg. 

Weight  at  start 71.090  Weight  at  end 70.160 

Water  drunk 1.0548         Carbon  dioxid 07383 

Water  in  respiration 0.8289 

Oxygen  absorbed 0.7709        Urine i-i975 

72.9247  72-9247 

'Pettenkofer  and  Voit:  "Zeitschrift  fur  Biologic,"  1866,  Bd.  ii,  p.  478. 


26  SCIENCE    OF   NUTRITION. 

The  analysis  of  the  urine  showed  12.51  grams  of  nitrogen 
and  8.25  grams  of  carbon.  A  calculation  gives  the  amount  of 
carbon  in  the  respiration  as  201.3  grams.  If  we  neglect  the  feces 
as  being  too  small  in  starvation  to  influence  the  results,  we  find 
that  the  total  carbon  elimination  for  twenty-four  hours  was 
209.55  grams,  and  the  total  nitrogen  12.51.  In  the  Liebig 
extract  ingested  there  were  2.44  grams  of  carbon  and  1.18  grams 
of  nitrogen,  which  must  be  deducted  from  the  above  in  order  to 
obtain  the  strict  loss  of  carbon  and  nitrogen  from  the  body  during 
the  period  of  starvation.     These  values  are: 

C 207.11  grams. 

N 11.33     " 

These  two  figures  enabled  Pettenkofer  and  Voit  to  calculate 
what  substances  had  burned  in  the  body.  As  every  gram  of 
nitrogen  in  the  excreta  is  approximately  represented  by  the 
destruction  of  6.25  grams  of  meat  protein,  the  amount  of  such 
protein  destroyed  by  the  man  was  70.81  grams.  It  has  been 
found  that  for  every  gram  of  nitrogen  present  in  meat  protein 
there  are  3.28  grams  of  carbon.  It  is  therefore  easy  to  estimate 
that  destruction  of  protein  represented  by  11.33  grams  of  nitro- 
gen involved  the  elimination  of  37.16  grams  of  carbon.  Now, 
the  man  eliminated  207.11  grams  of  total  carbon,  from  which 
this  protein  carbon  may  be  deducted,  leaving  as  residue  169.95 
grams,  which  must  have  originated  from  a  source  other  than 
protein.  The  possible  sources  are  two  in  number — carbohy- 
drates and  fats.  In  starvation  no  carbohydrates  are  ingested 
and  their  supply  in  the  form  of  reserve  glycogen  is  usually 
counted  as  being  negligible  in  such  experiments  as  these.  The 
only  other  source  from  which  the  169.95  grams  of  extra  carbon 
could  have  been  derived  is  fat,  and  as  fat  contains  76.52  per 
cent,  of  carbon,  a  destruction  of  222.1  grams  of  fat  may  be 
calculated.     This  fasting  man  therefore  destroyed: 

Protein 70.81  grams. 

Fat 222.1       " 

That  such  metabolism  actually  did  take  place  was  further 


INTRODUCTORY.  27 

indicated  by  the  comparison  of  the  amount  of  oxygen  needed  for 
the  destruction  of  the  above  constituents,  and  the  amount  of 
oxygen  absorption  as  determined  by  the  experiment. 

From  the  constituents  of  the  protein  and  fat  destroyed, 
Pettenkofer  and  Voit  deducted  the  constituents  of  the  urine, 
which  contains  part  of  the  C  and  H  belonging  to  protein.  The 
balance  of  the  carbon  and  hydrogen  was  fit  for  oxidation  to 
carbon   dioxid   and    water.     Their   calculation   may    thus    be 

'^  '  Weight  in  Grams. 

C  HO 

Composition  of  the  protein  burned 37-i6  5.8         17. i 

Composition  of  fat  burned 169.95  25.7         25.1 

Total  C,  H  and  O  metabolized 207.11  31.5         42.2 

Deduct  quantity  in  the  urine 8.2  2.0  7.6 

Balance  available  for  respiratory  CO2  and  HgO 19S.9  29.5         34.6 

Oxj'gen  required 530-4  235.7 

Total  O  required  for  the  formation  of  COj  and  HjO 766.1 

Less  O  in  the  protein  and  fat 34.6 

OxA-gen  actually  required 73i-5 

O.xj'gen  absorption  as  determined 779-9 


Difference. 


We  may  reach  the  same  result  by  using  the  most  modern 
figures  for  the  oxgyen  requirement  in  the  metabolism  of  the 
foodstuffs.  We  now  know  that  to  burn  loo  grams  of  meat 
protein  requires  133.43  grams  of  oxygen,  and  to  burn  100  grams 
of  fat  requires  288.5  grams,  and  to  burn  100  grams  of  starch 
1 18.5  grams.     This  being  true,  there  are  required: 

Oxygen. 

For  70.81  grams  protein 94-44  g- 

For  222.1        "      fat 639.5s  g. 


Total  required 733-99 

Oxygen  absorption  as  found 779-9 


Difference 45-91  g- 

Had  carbohydrates  burned,  less  oxygen  would  have  been 
needed,  since  carbohydrates  contain  a  larger  proportion  of 
oxygen  than  fats.     Had  the  extra  169.95  grams  of  carbon  been 


28  SCIENCE   OF   NUTRITION. 

due  to  the  combustion  of  starch  (or  glycogen),  382  grams  would 
have  burned,  requiring  452.7  grams  of  oxygen  instead  of  639.5 
grams  for  fat.  Pettenkofer  and  Voit  found  in  the  amount  of 
oxygen  absorption  a  confirmation  of  their  belief  that  the  fasting 
organism  supports  itself  by  the  combustion  of  its  own  protein 
and  fat. 

It  is  apparent  from  this  discussion  that  the  quantity  of 
oxygen  needed  in  metabolism  depetids  upon  the  kind  of  material 
that  burns  in  the  organism,  and  also  that  the  relation  between 
the  amount  of  oxygen  absorbed  and  carbon  dioxid  excreted 
depends  on  the  same  factor.  Regnault  and  Reiset  frequently 
observed  that  this  latter  relationship  was  variable.  The  ratio 
of  the  volume  of  carbon  dioxid  expired  to  the  volume  of  oxygen 
inspired  during  the  same  time  is  called  the  respiratory  quotient. 
When  carbohydrates  burn,  the  R.  Q.  is  unity;  that  is,  for  every 
hundred  volumes  of  carbon  dioxid  excreted  a  hundred  volumes 
of  oxygen  are  absorbed.  When  protein  burns  the  quotient  is 
y°|"  Q^"  =  ^  or  0.781,  and  when  fat  burns  the  quotient  is  0.71. 
Pettenkofer  and  Voit  calculated  that  the  respiratory  quotient  in 
their  fasting  man  was  0.69.  This  indicated  a  combustion  of  fat 
in  the  organism. 

The  further  researches  of  Pettenkofer  and  Voit  were  founded 
on  the  principles  described  in  the  above  experiment  on  a  fasting 
man.  If  meat  and  fat  were  ingested,  the  carbon  and  nitrogen 
excreta  were  collected,  and  from  these  data  it  was  determined 
how  much  of  each  foodstuff  was  oxidized  and  whether  there  was 
a  storage  of  either  in  the  body  or  a  loss  of  either  from  the  body. 
If  a  mixed  diet  which  included  carbohydrates  were  given,  the 
carbon  dioxid  elimination  increased  and  the  oxygen  absorption 
was  such  as  indicated  the  combustion  of  carbohydrates.  It  was 
assumed  that  after  deducting  the  protein  carbon  from  the  total 
carbon  eliminated,  the  balance  of  extra  carbon  was  derived 
from  the  destruction  of  the  carbohydrates  in  so  far  as  these  were 
ingested;  any  carbon  in  excess  of  this  was  attributed  to  fat 
combustion. 


INTRODUCTORY.  29 

Voit*  in  his  necrolog}'  of  Pettenkofer  writes:  "Imagine  our 
sensations  as  the  picture  of  the  remarkable  processes  of  the 
metabohsm  unrolled  before  our  eyes,  and  a  mass  of  new  facts 
became  kno^^•n  to  us!  We  found  that  in  starvation  protein  and 
fat  alone  were  burned,  that  during  work  more  fat  was  burned, 
and  that  less  fat  was  consumed  during  rest,  especially  during 
sleep;  that  the  carnivorous  dog  could  maintain  himself  on  an 
exclusive  protein  diet,  and  if  to  such  a  protein  diet  fat  were 
added,  the  fat  was  almost  entirely  deposited  in  the  body;  that 
carbohydrates,  on  the  contrary,  were  burned  no  matter  how 
much  was  given,  and  that  they,  like  the  fat  of  the  food,  protected 
the  body  from  fat  loss,  although  more  carbohydrates  than  fat  had 
to  be  given  to  effect  this  purpose;  that  the  metabolism  in  the 
body  was  not  proportional  to  the  combustibility  of  the  substances 
outside  the  body,  but  that  protein,  which  burns  with  difficulty 
outside,  metabolizes  with  the  greatest  ease,  then  carbohydrates, 
while  fat,  which  readily  burns  outside,  is  the  most  difficultly 
combustible  in  the  organism." 

Since  the  days  of  these  researches  repeated  experiments 
have  established  the  verity  of  the  conclusions  drawn.  It  is 
interesting  to  note  that  among  the  earliest  experiments  made 
were  some  upon  patients  in  pathological  conditions,  one  suffer- 
ing from  leukemia,  another  from  diabetes. 

Besides  the  influence  of  foods  upon  metabolism,  the  changes 
brought  about  by  exercise,  temperature,  and  drugs  were  in- 
vestigated, not  only  by  the  Munich  school,  but  by  many  other 
workers.     Similar  investigations  are  actively  progressing  to-day. 

Among  the  important  conclusions  reached  by  Voit  was  that 
concerning  the  manner  of  the  metabolism.  It  has  been  stated 
that  Liebig  believed  that  fat  and  carbohydrates  were  destroyed 
by  oxygen,  while  protein  metabolism  took  place  on  account  of 
muscle  work. 

Voil^   showed   thai   muscle   work   did   not   increase   protein 

'Voit:   "Zeitschrift  fiir  Biologic,"  1901,  Bd.  xli,  p.  i. 

'Voit:   "Zeitschrift  fiir  Bioiogie,"  1869,  Bd.  v,  p.  169;   Bd.  ii,  1866,  p.  535. 


30  SCIENCE    OF   NUTRITION. 

metabolism  and  that  the  metabolism  was  not  proportiofial  to 
the  oxygen  supply.  The  oxygen  absorption  apparently  de- 
pended upon  what  metabolized  in  the  cells.  Voit  believed 
that  the  cause  of  metabolism  was  unknown,  that  the  process 
was  one  of  cleavage  of  the  food  molecules  into  simpler  pro- 
ducts, which  could  then  unite  with  oxygen.  Yeast  cells,  for 
example,  convert  sugar  into  carbonic  acid  and  alcohol  with- 
out the  intervention  of  oxygen.  In  like  manner  the  first  pro- 
ducts of  the  decomposition  of  fat,  sugar  and  protein,  are 
formed  in  metabolism  through  unknown  causes.  Some  of 
these  preliminary  decomposition  substances  may  unite  with 
oxygen  to  form  carbon  dioxid  and  water,  others  may  be  converted 
into  urea,  while  others  under  given  circumstances  may  be  syn- 
thesized to  higher  compounds.  In  any  case  the  absorption  of 
oxygen  does  not  cause  metabolism,  but  rather  the  amount  of  the 
metabolism  determines  the  amount  of  oxygen  to  be  absorbed.     (See 

P-  3I-) 

The  statement  is  frequently  met  with  in  the  literature  of  the 

subject  that  such  and  such  a  disease  is  the  consequence  of  de- 
ficient oxidative  power  in  the  tissues.  For  example,  it  has 
recently  been  stated  that  alcohol  decreases  the  oxidative  power 
of  the  liver  for  uric  acid.^  Such  apparent  decrease  in  oxidative 
power  may,  however,  be  due  to  the  fact  that  the  normal  oxidiz- 
able  cleavage  products  are  not  formed  and  therefore  no  oxida- 
tion can  take  place.  It  is  not  due  to  lack  of  oxygen  that  sugar 
is  not  oxidized  in  diabetes,  or  cystin  in  cystinuria.  There  is  the 
normal  supply  of  oxygen  present,  but  the  cleavage  of  these 
substances  into  bodies  which  can  unite  with  oxygen  cannot  be 
effected,  and  hence  they  cannot  be  metabolized. 

Voit's  pupil,  Lossen,^  showed  that  the  carbon  dioxid  elimina- 
tion in  respiration  was  independent  of  the  ventilation  of  the  lungs 
except  in  so  far  as  forced  breathing  increased  the  muscular  work 
and  the  consequent  output  of  carbon  dioxid. 

^Beebe,  S.  P.:   "American  Journal  of  Physiology,"  1904,  vol.  xii,  p.  36. 
^Lessen:   " Zeitschrif t  fiir  Biologic,"  1S66,  Bd.  ii,  p.  244;  and  1870,  Bd.  vi, 
p.  298. 


IXTRODUCTORY.  3 1 

Pfliiger/  who  through  different  reasoning  came  to  the  same 
conclusion  as  Voit,  devised  an  experiment  in  which  a  rabbit 
breathed  quietly  through  a  cannula,  and  the  oxygen  absorption 
was  compared  with  that  of  the  same  animal  when  rapid  artificial 
ventilation  of  the  lungs  with  air  took  place,  producing  apnea  or 
hyperarterialization  of  the  blood.  There  was  no  difference, 
as  is  seen  from  the  following  table: 


Oxygen  Absorbed  in  C.C.  During  is  Minutes. 

Normal  respiration. 

Apnea. 

Series  I 

20I.66 
203.21 

203.88 
210.47 

Series  II         

From  these  experiments  it  is  made  sure  that  the  respiration 
does  not  cause  or  regulate  metabolism.  On  the  contrary,  the 
metabolism  regulates  the  respiration.  The  metabolism  of.  the 
tissues,  through  its  oxygen  requirement  and  its  carbon  dioxid 
production,  changes  the  condition  of  the  blood  and  thereby  regu- 
lates the  respiration.  These  distinctions  are  oj  fundamental 
importance. 

Thus  far  the  history  of  the  principles  which  underlie  the 
exact  measurement  of  the  metabolism  has  been  briefly  given. 
By  metabolism  is  meant  the  chemical  changes  of  materials  under 
the  influence  of  living  cells.  The  first  cause  of  these  chemical 
changes,  it  has  been  seen,  is  unkno^vn,  but  their  results  lead  to 
motions  of  the  smallest  particles  of  protoplasm,  motions  whose 
totality  we  call  life.  Phenomena  of  life  are  phenomena  of 
motion,  due  to  liberation  of  energy  in  the  breaking  down  of 
molecules.  The  motions  are  principally  manifested  as  heat, 
mechanical  energy,  and  electric  currents.  In  the  organism 
mechanical  energy  may  be  converted  into  heat,  as  appears  when 
the  work  of  the  heart  is  converted  into  heat  by  the  friction  of  the 
blood  upon  the  capillaries.     Also  the  current  of  electricity  de- 

*  Pfliiger:  " Archiv  fiir  die  ges.  Physiologie,"  1877,  Bd.  xiv,  p.  i. 


32  SCIENCE   OF   NUTRITION. 

veloped  at  each  systole  of  the  heart,  or  in  any  other  active  tissue, 
is  resolved  into  heat.  Thus  heat  may  become  a  measure  of  the 
total  activity  of  the  body.  It  is  derived  from  the  total  metabo- 
lism and  must  be  dependent  on  it  and  be  a  measure  of  it.  Hence 
the  physical  activities  noted  in  life  are  the  results  of  chemical 
decompositions.  Metabolism  vivifies  the  energy  potential  in 
chemical  compounds. 

Lavoisier^  was  the  first  to  recognize  that  animal  heat  was 
derived  from  the  oxidation  of  the  body's  substance  and  to  com- 
pare animal  heat  to  that  produced  by  a  candle.  To  prove  this 
he  burned  a  known  quantity  of  carbon  in  an  ice-chamber  and 
noted  the  amount  of  ice  melted.  He  then  calculated  the  amount 
of  heat  produced  from  a  unit  of  carbon.  He  and  La  Place  put 
a  guinea-pig  in  an  ice-chamber  and  noted  the  amount  of  ice 
which  melted  during  ten  hours  and  calculated  the  heat  given 
off  from  the  animal.  They  then  determined  how  much  carbon 
dioxid  the  guinea-pig  gave  off.  The  animal  yielded  31.82 
calories  to  the  ice-chamber,  while  a  calculation  from  the  respira- 
tory analysis  showed  that  25.408  calories  could  have  been 
derived  by  the  burning  of  enough  carbon  to  yield  the  same 
amount  of  carbon  dioxid  as  was  eliminated  by  the  animal. 

Lavoisier  realized  several  of  the  errors  in  his  work.  For 
example,  the  calorimetric  determination  on  the  animal  was 
made  at  a  diff'erent  temperature  from  that  of  the  respiratory 
experiment,  and  Lavoisier  knew  that  cold  would  raise  the 
carbon  dioxid  output.  Also  cold  reduced  the  heat  in  the  animal 
itself,  and,  further,  the  water  of  respiration  was  added  to  that 
of  the  melting  ice.  But  Lavoisier  concluded  that  the  source 
of  the  heat  lay  in  the  oxidation  of  the  body. 

Crawford,  in  England,  found  after  burning  wax  and  carbon, 
or  on  leaving  a  live  guinea-pig  in  his  water  calorimeter,  that  for 
every  hundred  ounces  of  oxygen  used  the  water  was  raised  the 
following  number  of  degrees  Fahrenheit: 

^For  this  literature  see  Rubner:  " Zeitschrif t  fiir  Biologie,"  1893,  Bd.  xxx, 
P-  73- 


INTRODUCTORY,  33 

Wax 2.1 

Carbon 1.93 

Guinea-pig 1.73 

Crawford  concluded  that  the  heat  above  produced  was  due  to 
the  transformation  of  pure  air  into  fixed  air  (carbon  dioxid)  and 
water. 

The  method  of  Crawford  was  in  reality  one  of  considerable 
accuracy.  According  to  the  modern  computation  of  Zuntz  and 
Hageman/  the  following  are  the  values  of  heat  production 
where  one  liter  of  oxygen  is  used  to  burn  the  different  food- 
stuffs in  the  body: 

Calories. 

I  liter  of  oxygen  used  in  the  metabolism  of  protein  yields 4.691 

I     "     "       '"  "       "  "         "  fat  "       4.686 

I     "     "       "  "       "  "         "  starch       "       5.046 

This  table  shows  that  there  is  a  maximum  variation  of  only 
7  per  cent,  in  the  heat  value  of  a  unit  of  oxygen  to  the  body. 
Hence  the  quantity  of  oxygen  absorbed  may  be  utilized  as  an 
approximate  indicator  of  heat  production  (Fig.  lo,  p.  322). 

In  1823  the  French  Academy  offered  a  prize  for  the  best 
essay  on  the  subject  of  animal  heat.  Depretz  and  Dulong 
competed  for  the  prize  and  it  was  awarded  to  the  former. 

Depretz^  calculated  the  amount  of  heat  which  would  have 
been  liberated  in  burning  the  carbon  and  hydrogen  of  the  metab- 
olism to  carbon  dioxid  and  water,  and  compared  this  with  the 
amount  of  heat  given  off  by  the  animal.  The  heat  as  calculated 
was  only  74  to  90  per  cent,  of  what  was  found,  a  discrepancy 
due  to  faults  in  the  method  employed  (see  p.  42).  So  Depretz 
concluded  that  although  the  respiration  was  the  principal  source 
of  animal  heat,  food,  the  motion  of  the  blood,  aiid  friction 
yielded  the  remainder.  Interpretation  along  the  lines  of  the  law 
of  the  conservation  of  energy  was  obviously  beyond  the  ideas  of 
the  time. 

Dulong's^  experiments  also  led  to  the  same  conclusion,  that 

'Zuntz  and  Hageman:   "Stoffwechsel  des  Pferdes,"  1898,  p.  245. 
*  Depretz:    "Annal.   de   chim.   et  do  phys.,"    1824. 
'Dulong:   Ibid.,  1841. 
3 


34  SCIENCE    OP   NUTRITION. 

oxidation  was  insufi&cient  to  explain  the  cause  of  animal  heat, 
and  that  there  must  be  other  sources  of  it. 

In  1 85 1  R.  Mayer  laid  down  the  law  of  the  conservation  of 
energy,  and  Helmholtz  demonstrated  its  general  applicability. 

Energy  cannot  arise  from  nothing,  nor  can  energy  disappear 
into  nothing.  Where  energy  is  active  it  must  have  been  else- 
where potential.  The  sum  total  of  energy  remains  constant  in 
the  universe,  but  energy  may  vary  in  kind.  The  kinds  include 
mechanical  energy,  heat,  electricity,  magnetism,  and  potential 
energy.  The  source  of  energy  on  the  earth  is  the  sun,  except- 
ing the  energy  of  the  tides,  which  is  due  principally  to  the 
moon.  The  sun  unevenly  warms  the  atmosphere,  producing 
winds  which  drive  ships  and  windmills.  The  sun's  heat  lifts 
the  vapor  of  water  into  the  atmosphere,  producing  rain,  in 
consequence  of  which  rivers  are  made  to  turn  machinery.  The 
sunlight  acts  upon  a  mixture  of  hydrogen  and  chlorin  gas,  caus- 
ing them  to  unite  with  a  loud  explosion,  and  the  sun  acts  upon 
the  green  leaf  of  the  plant,  causing  it  to  unite  carbon  dioxid  and 
water,  with  the  production  of  formic  aldehyde,  which  is  built  up 
into  sugar,  oxygen  being  given  off  in  the  process.  The  sun's 
energy  required  to  build  up  the  compound  becomes  latent  or 
potential  in  it.  Whenever  and  wherever  this  sugar  is  again  con- 
verted into  carbon  dioxid  and  water  by  oxidation,  exactly  the 
same  quantity  of  energy  taken  from  the  sun  and  made  potential  in 
the  sugar  is  set  free.  This  sugar  in  the  plant  may  be  further  con- 
verted into  starch,  cellulose,  fat,  and  possibly  into  protein. 
Plants  furnish  wood  and  coal  as  fuel  for  the  steam-engine. 
They  also  furnish  the  basis  of  animal  food,  yielding  substances 
which  can  build  up  animal  tissues,  and  which  can  furnish  the 
energy  necessary  to  maintain  those  motions  in  the  cells  whose  ag- 
gregate is  called  life.  These  motions  appear  in  the  body  as  heat, 
mechanical  work,  and  electric  currents,  all  of  which  may  be 
measured  as  heat.  Is  this  energy  completely  derived  from  the 
metabolism?  This  question  is  but  the  continuation  of  the  old 
one  of  Lavoisier  in  the  li2;ht  of  newer  science. 


INTRODUCTORY.  35 

Bischoff  and  Voit^  in  iS6o  still  calculated  the  heat  value  of 
the  metabolism  from  the  heat  developed  in  burning  the  carbon 
and  hydrogen  elements  of  the  metabolism.  They  recognized, 
however,  that  this  was  a  false  method,  and  stated  that  they 
should  employ  the  calorific  value  of  fat,  starch,  and  protein, 
less  the  urea,  since  they  recognized  that  urea  was  capable  of 
undergoing  combustion  with  liberation  of  heat. 

In  i860  Voit^  took  a  Thomson  calorimeter  with  him  from 
London  to  Munich.  After  Franldand's  determination  of  the 
heat  value  of  the  various  foodstuffs  and  urea  Voit^  prepared  a 
table  in  1866  for  use  in  his  lectures  showing  that  the  metabolism 
of  the  fasting  man  experimented  on  by  Pettenkofer  and  Voit 
indicated  the  production  of  2.25  million  small  calories,  while 
the  metabolism  on  a  medium  diet  was  2.40  million  calories. 

In  1873  Pettenkofer  and  \"oit*  calculated  that  100  grams 
of  fat  were  the  physiological  equivalent  of  175  grams  of  starch. 
Liebig  at  that  time  had  suggested  that  the  amount  of  these 
substances  which  could  be  burned  by  a  man  was  proportional 
to  the  oxygen  supply. 

Voit,  not  content  with  his  results,  suggested  to  Schiirmann 
in  1878-79  that  he  carry  on  experiments  to  see  in  what  way 
carbohydrates  and  fat  were  interchangeable  in  nutrition.  Schiir- 
mann died  before  the  work  was  completed  and  the  investigation 
was  continued  by  Rubner.  The  isodynamic  lan',  which  showed 
that  the  foodstuffs  replaced  each  other  in  accordance  with  their 
heat- producing  value,  was  the  result. 

Rubner  gives  the  following,  as  the  quantities  of  the  different 
foodstuffs  which  are  isodynamic: 
100  g.  fat. 
232  g.  starch 
234  g.  cane  sugar 
243  g.  dried  meat. 

Bischoff  and  Voit:   "Die   Gcsetze  der  Ernahrung  des  Fleischfressers," 
i860,  p.  43. 

*Voit:   "Munchcner  medizinische  Wochenschrifl,"  1902,  Bd.  xlix,  p.  233. 

'  Voit:   Loc.  cit. 

*  Pettenkofer  and  Voit:   "Zeilschrift  fiir  Biologic,"  1873,  Bd.  ix,  \).  534. 


36  SCIENCE    OF   NUTRITION. 

After  Stohmann^  published  his  research  on  the  calorific 
value  of  foods,  urea,  etc.,  Voit  commenced  the  construction  of 
a  calorimeter  for  the  measurement  of  the  heat  eliminated  from 
the  body  of  a  man  whose  metabolism  was  simultaneously  de- 
termined. The  results  obtained  by  the  use  of  this  machine  have 
never  been  published. 

Rubner^  in  Voit's  laboratory  during  this  same  period  was 
making  a  series  of  valuable  calorimetric  determinations.  The 
heat  value  to  the  body  of  burning  starch  and  fat  were  obviously 
the  same  as  that  determined  in  the  calorimeter,  since  in  both 
cases  the  same  end-products,  carbon  dioxid  and  water,  resulted. 
The  heat  value  of  protein  in  the  calorimeter  was  different  from 
its  fuel  value  to  the  body,  since  the  end-products  were  different 
in  the  two  cases.  When  protein  is  oxidized  in  the  body,  the 
products  of  its  metabolism  are  lost  in  three  different  ways — 
through  the  respiration,  urine,  and  feces.  The  last  two  contain 
latent  heat  lost  to  the  body,  which  must  be  deducted  from  the 
heat  value  of  protein  determined  calorimetrically. 

The  custom  of  Stohmann  and  previous  authorities  had  been 
to  deduct  the  heat  value  of  urea  from  the  heat  value  of  protein, 
in  order  to  obtain  the  actual  physiological  or  fuel  value  of  pro- 
tein, for  the  organism.  But  in  the  earliest  experiments  of 
Pettenkofer  and  Voit^  it  was  recognized  that  in  starvation 
and  after  the  ingestion  of  meat,  there  was  a  much  larger 
output  of  carbon  in  the  urine  than  corresponded  to  the  quantity 
of  urea  present.  The  ratio  of  nitrogen  to  carbon  was  nearly 
constant  in  the  urine  when  the  conditions  of  feeding  were  similar. 
If  urea  alone  were  present,  Rubner  estimated  there  would  be 
0.429  gram  of  C  to  i  of  N  or  an  N  :  C  =  i :  0.429.  In  starvation 
the  urine  contains  extractive  nitrogen  (creatinin,  uric  acid,  etc., 
having  relatively  more  carbon  than  urea)  which  has  been  de- 


^  Stohmann:    "Journal  fiir  praktische  Chemie,"  1885,  Bd.  xxxi,  p.  273,  and 
earlier  papers. 

^Rubner:   "Zeitschrift  fiir  Biologie,"  1885,  Bd.  xxi,  pp.  250  and  337. 
^Pettenkofer  and  Voit:  Ihid.,  1866,  Bd.  ii,  p.  471. 


INTRODUCTORY. 


37 


rived  from  the  breaking  do-\\Ti  of  tissue  protein,  and  the  ratio  is 
N  :  C  =  1 :  0.728.  When  meat  was  ingested  the  fact  that  the  food 
contained  these  extractives  made  the  C  :  N  ratio  0.610.  And 
even  after  six  days'  ingestion  of  meat  washed  free  from  extract- 
ives the  urine  of  the  seventh  and  eighth  days  still  showed  an 
elimination  of  carbon  other  than  that  due  to  urea,  as  was  indi- 
cated by  the  ratio  0.532.  Therefore,  from  the  metabolism  fol- 
lowing the  ingestion  of  the  proteins  of  washed  meat  small 
amounts  of  carbon  compounds  other  than  urea  are  eliminated 
in  the  urine. 

Rubner  saw  that  it  was  the  heat  value  of  the  urinary  con- 
stituents themselves  which  had  to  be  subtracted  from  the  heat 
value  of  protein  if  the  fuel  value  of  protein  to  the  body  was  to  be 
determined. 

The  following  table  shows  Rubner's  results  after  burning 
the  drv  urine: 


CALORIC  VALUE  OF  URINE. 

Material  Bxjrnzd. 

C:N. 

Calories 
FROM  I  Gram. 

Calorific  Value 
OF  I  Gram  N. 

Urea 

0.429 

0-532 
0.610 
0.728 

2.523 
2.706 

2.954 
3.101 

5-41 
5.69 
7.46 

8.49 

Urine  after  feeding  protein 

Urine  after  feeding  meat 

Urine  in  starvation 

It  was  not  alone  necessary  to  know  the  heat  value  of  the 
urine  excreted,  but  also  that  of  the  feces.  Rubner  found  that 
after  giving  100  parts  of  dry  muscle  containing  5.5  grams  of 
ash  there  was  an  elimination  of  38.2  grams  of  the  organic  part 
in  the  urine  and  2.7  grams  in  the  feces.  The  following  table 
represents  this  division  of  material  in  the  excreta: 

c.             H.            N.  o. 

Composition  of  loo  parts  dry  muscle 50.5  7.6  15.4  20.97 

Urine  contains  38.2  parts 9.63  2.52  15.16  10.9 

Feces  contain  2.7  parts 1.67  0.25  0.24  0.54 

Excreted  in  urine  and  feces 11.30         2.77         1540         ii-44 

Balance  for  respiration 39.2  4.8  9.53 


38  SCIENCE    OF   NUTRITION. 

Rubner  determined  the  amount  of  heat  produced  from  i 
gram  of  ash-free  feces  after  meat  ingestion  and  found  it  to  be 
6.127  calories,  while  i  gram  of  ash-free  feces  after  protein 
(washed  meat)  ingestion  yielded  6.852  calories.  The  total  calo- 
rific value  of  one  gram  of  beef  muscle  when  Rubner  burned  it 
in  the  calorimeter  was  5.345  calories.  He  had  now  the  principal 
data  required  to  determine  its  heat  value  in  the  body.  If  from 
100  grams  of  meat  2.6  grams  appear  as  feces  having  a  calorific 
value  of  6.127  calories  per  gram,  then  there  is  here  a  loss  of 
6.127  X  2.7  =  16.83  calories.  If  from  every  100  grams  of  meat 
containing  15.4  grams  of  nitrogen  15.16  grams  of  the  latter 
appear  in  the  urine  and  such  urine  produced  by  ingesting  meat 
has  a  calorific  value  of  7.46  calories  for  every  gram  of  nitrogen 
present,  then  the  energy  loss  in  the  urine  would  be  7.46  X 
15.16  =  112.94  calories.  For  dry  muscle  substance  we  find 
therefore : 

Calories. 
100  grams  muscle 534-5 

Wa^te  I   ^""^^ "^-94  \  Total  12077 

waste  <^  P^^g^ 16.83     /    -^^^^^ "9-77 

Fuel  value  of  100  grams  of  dr}'. muscle 404-73 

From  this  value  there  must  be  a  slight  deduction  for  the  heat 
present  in  the  protein  in  its  colloidal  state  but  lost  on  drying,  and 
for  the  heat  of  solution  necessary  to  dissolve  urea  and  other 
urinary  constituents.     Rubner  estimates  these  as: 

Heat  for  the  imbibition  of  protein 2.688 

Heat  for  solution  of  urea 1.989 

4.677 

Subtracting  4.67  from  404.73  leaves  400.06  calories  as  the 
maximum  of  energy  obtainable  from  100  grams  of  the  dried 
solids  of  meat.  The  calorimeter  shows  a  heat  value  of  534.5 
calories  for  the  same  protein.  Of  this,  400.06  calories,  or  74.9 
per  cent.,  are  available  in  the  organism,  while  the  remainder, 
or  25  per  cent.,  goes  to  waste. 

A  further  calculation  shows  that  every  gram  of  nitrogen  in  the 


INTRODUCTORY. 


39 


urine  and  feces  represents  an  elimination  of  heat  from  protein 
metabolism  equal  to  25.98  calories.  The  heat  value  of  protein 
under  the  different  physiological  conditions  was  estimated  by 
Rubner  after  the  above  fashion,  and  may  thus  be  tabulated: 

CALORIFIC  VALUE  OF  PROTEIN  IN  NUTRITION. 


Calokies  Yielded 
BY  Metabolism 
OF  100  Grams  of 
Protein  in  the 
Body. 


Heat  Value  in 
Calories  of  Pro- 
tein Metabolism 
Yielding  i  Gm.  or 
N.  IN  THE  Ex- 
creta. 


After  protein  (washed  meat)  ingestion 

After  meat  ingestion 

Starvation 


26.66 
25.98 
24.98 


If  we  know  the  amount  of  nitrogen  in  the  excreta  we  can 
calculate  from  these  standard  figures  of  Rubner  the  heat  value 
of  the  protein  metabolism  to  the  body.  Rubner  found  that  the 
heat  value  of  i  gram  of  pig's  fat  (lard)  was  9.423  calories. 
Since  fat  contains  76.5  per  cent,  of  carbon,  it  could  be  calcu- 
lated that  for  every  gram  of  carbon  eliminated  in  the  respiration, 
which  was  the  result  of  fat  metabolism,  12.3  calories  must  have 
been  liberated  in  the  body.  These  figures  enabled  Rubner  to 
calculate  the  amount  of  heat  liberated  by  the  fasting  man  of 
Pettenkofer  and  Voit,  whose  metabolism  we  have  already  dis- 
cussed. The  N  excreted  was  multiplied  by  24.98  and  the  fat 
carbon  by  12.3  which  gave  the  total  heat  value  of  the  period: 

Heat  from  protein  (11.33  Gm.  N  X  24.98) 283  Cal. 

Heat  from  fat  (169.95  C  X  12.3) 2091  Cal. 

Total  heat  value  of  the  metabolism  as  calculated. .  .2374  Cal. 

Rubner  applied  such  calculations  as  these  to  the  material  at 
hand  in  the  literature  of  the  time,  and  discovered  that  the  heat 
value  0}  the  metabolism  of  the  resting  individual  is  proportional 
to  tht  area  of  the  surjace  0}  his  body.  For  example,  a  man  in  star- 
vation, or  on  a  medium  diet,  an  infant  at  the  breast,  and  a 
starving  dog,  were  shown  to  give  off  similar  quantities  of  heat 


40  SCIENCE    OF   NUTRITION. 

per  square  meter  of  surface.  To  these  Rubner  subsequently 
added  the  results  of  his  researches  upon  a  dwarf.  The  follow- 
ing tables  illustrate  this  point : 

Yield  of  Calories  per  Sq.  M. 
Surface  in  24  Hours. 

Adult  man  in  starvation 1 134 

Dog  in  starvation 11 12 

Adult  man  on  a  medium  mixed  diet 1 189 

Breast-fed  infant 1221 

Dwarf  (weight  =  6.6  Kg.)  medium  mixed  diet 1231 

This  law,  that  the  resting  animal  in  starvation  or  on  a  me- 
dium diet  gives  off  the  same  quantity  of  heat  per  square  meter  of 
surface,  can  be  extended  so  that  it  applies  to  all  warm-blooded 
animals.  Thus  E.  Voit'^  has  collected  data  for  the  following 
table : 

Calories. 

Weight  in  Kg.  Per  Kilo.  Per  Sq.  M.  Surface . 

Pig 128.0  19. 1  1078 

Man 64.3  32.1  1042 

Dog 15.2  51.5  1039 

Goose 3.5  66.7  967 

Fowl 2.0  71.0  947 

Mouse 0.018  1188 

Rubner  from  his  work  on  protein  considered  that  the 
heat  value  of  i  gram  in  an  average  mixed  diet  might  well  be 
placed  at  4.1  calories.  Of  course,  such  a  mixed  diet  would 
contain  casein  (4.4  cal.),  the  organic  substance  of  meat  (4.233 
caL),  and  vegetable  proteins  (3.96  cal.).  The  daily  food 
allowance  for  animal  protein  was  put  at  60  per  cent.,  for  vege- 
table protein  at  40  per  cent.,  of  the  total  protein  in  the  mixed 
dietary.  For  the  value  of  neutral  fats  Stohmann's  figures  for 
olive  oil,  animal  fat,  and  butter  fat  were  averaged  as  follows : 

Olive  oil 9-384  Calories  per  Gm. 

Animal  fat 9-372         "         "       " 

Butter  fat 9.179         "         "       " 

Average 9-3^2         "         "       " 

For  the  heat  value  of  one  gram  of  fat  in  a  mixed  diet  Rubner 
therefore  adopted  the  value  9.3. 

^E.  Voit:   "Zeitschrift  fiir  Biologic,"  1901,  Bd.  xli,  p.  120. 


INTRODUCTORY.  4I 

The  following  heat  values  have  been  found  for  carbohydrates : 

Stohmann.         Rubner. 

Dextrose 3.692  3.755 

Milk  sugar 3-877 

Cane  sugar 3-959  4.001 

Starch 4.1 16 

Considering  the  predominating  importance  of  starch  in  the 
average  diet,  Rubner  gave  the  value  of  4.1  to  the  group  of 
carbohydrates  in  the  foods. 

Rubner's  "standard  values"  have  been  widely  used  through- 
out the  world  in  determining  the  average  fuel  value  of  a  mixed 
diet.     They  are : 

I  gram  of  protein 4.1  calories 

I  gram  of  fat 9.3  calories 

I  gram  of  carbohydrate 4.1  calories 

Their  accuracy  has  been  lately  verified  by  Rubner  ^  in  the  most 
careful  manner. 

Atwater  and  Bryant^  have  sought  to  modify  this  standard 
value  and  offer  the  following  in  substitution: 

I  gram  of  protein 4.0  calories 

I  gram  of  fat 8.9  calories 

I  gram  of  carbohydrate 4.0  calories 

Atwater^  states  that  these  figures  are  perfectly  accurate 
in  computing  the  average  diet  (results  of  411  experiments).  The 
difference  between  the  two  standards  probably  lies  in  the  fact 
that  Rubner  gave  comparatively  pure  foods,  while  the  waste 
through  the  feces  in  Atwater's  diets  reduced  the  nutritive  avail- 
ability. Another  difference  lies  in  the  fact  that  Atwater'*  uses 
as  a  small  calorie  the  amount  of  heat  necessary  to  raise  i  c.  c.  of 
water  from  a  temperature  of  19.5°  to  20.5°  instead  of  from  0° 
to  1°,  the  unit  ordinarily  employed. 

'Rubner:  "Zeitschrift  fiir  Biologie,"  Festschrift  zu  Voit,  1901,  Bd.  xlii, 
p.  261. 

*  Atwater  and  Br>'anl :  "Report  of  the  Storrs  Agricultural  Experiment 
Station,"  1899,  p.  no. 

*.\twater:  "Am.  Journal  of  Physiology,"  1904,  vol.  x,  "Proceedings  of  the 
Am.  Physiol.  Society,"  p.  xxx. 

*  Atwater  and  Rosa:  U.  S.  Dept.  of  Agriculture,  Bulletin  63,  1899,  p.  55. 


42 


SCIENCE    OF   NUTRITION. 


Rubner/  still  working  in  the  Munich  laboratory,  showed 
that  if  the  diet  were  increased  from  a  medium  to  an  abundant 
amount,  the  metabolism  as  indicated  by  the  heat  production 
rose.  This  dynamic  action  resulting  from  the  excessive  inges- 
tion of  a  foodstuff  was  greatest  with  protein,  less  after  fat,  and 
scarcely  in  evidence  after  carbohydrates. 

Finally  Rubner,  in  his  own  laboratory  at  Marburg,  evolved 
an  animal  calorimeter  which  could  accurately  measure  the 
amount  of  heat  a  dog  produced  in  twenty-four  hours.  The 
dog  was  placed  within  the  chamber  of  the  calorimeter,  and  this 
chamber  was  attached  to  a  respiration  apparatus,  so  that  the 
metabolism  could  be  calculated  according  to  the  method  of 
Pettenkofer  and  Voit.  From  the  metabolism  the  heat  produc- 
tion could  be  estimated.  The  results  were  a  triumphant 
demonstration  of  the  truth  of  the  law  of  the  conservation  of 
energy.  The  amount  of  heat  that  Rubner^  calculated  should 
have  been  derived  from  the  metabolism  of  the  dog  during  the 
day  spent  in  the  calorimeter  was  the  amount  actually  given  off  by 
the  dog  to  the  calorimeter.  The  metabolism,  the  cause  of  the 
motions  of  life,  was  the  source  of  the  heat-loss  of  the  body.  The 
results  achieved  constitute  a  final  verification  of  the  methods  of 
calculating  the  total  metabolism  originated  by  Pettenkofer  and 
Voit. 

An  epitome  of  Rubner's  experiments  is  here  presented: 


COMPARISON  OF  ESTIMATED  HEAT  FROM  METABOLISM  \\TTH 
HEAT  ACTUALLY  PRODUCED. 


Food. 


Starvation 

Fat 

Meat  and  fat. 

Meat 


Number  of 
Days. 


Heat  Calcu- 
lated FROM 
Metabolism. 


1296.3 
1091 
1510 
2492 

3985 
2249 
4780 


Heat  Directly 
Determined. 


1305-2 
1056.6 
1498.3 
2488.0 

3958-4 
2276.9 

4769-3 


Difference 
in  Percen- 
tage. 


-1.42 
-0.97 


—0.42 
+0.43 


^Rubner:   " Sitzungsberichte  der  bayer.  Akademie,"  1885,  p.  454. 
^Rubner:   "Zeitschrift  ftir  Biologic,"  1893,  Bd.  xx.x,  p.  73. 


INTRODUCTORY.  43 

Following  Rubner,  Atwater,  at  one  time  a  pupil  of  Voit, 
with  the  aid  of  Rosa,  the  physicist,  has  constructed  a  large 
calorimeter  capable  of  measuring  to  a  nicety  the  amount  of  heat 
given  off  by  a  man  living  in  it.  This  apparatus  has  confirmed 
Rubner's  experiments  and  has  shown  that  the  energy  expended 
by  a  man  in  doing  any  work,  such  as  bicycle-riding,  is  exactly 
equal  to  the  energy  set  free  by  metabolism  in  the  body.  Ex 
nihil 0  nihil  fit. 

This  apparatus  was  the  product  of  many  years  of  labor  and 
its  cost  was  borne  by  the  United  States  Government.  Armsby 
has  completed  a  similar  one  for  use  with  cattle,  for  the  Agricul- 
tural Station  of  the  State  of  Pennsylvania.  Benedict  with 
great  success  has  extended  Atwater's  work  in  the  notable 
Nutrition  Laboratory  of  the  Carnegie  Institution  in  Boston. 
This  is  housed  in  a  new  building  splendidly  equipped  with 
apparatus  for  the  simultaneous  determination  of  metabolism 
and  heat  production.  These  elaborate  and  costly  devices 
prove  and  confirm  the  general  laws  of  metabolism  in  the  body, 
through  a  knowledge  of  which  alone  proper  systems  of  nutrition 
for  people  under  various  conditions  may  be  devised.  The 
American  Indian  when  first  shown  a  watch  thought  it  was 
alive.  We,  on  the  other  hand,  have  come  to  look  upon  the 
living  organism  as  a  machine.  Like  the  moving  locomotive, 
we  bum  more  if  we  are  to  attain  a  faster  speed,  or  if  we  are 
to  keep  all  parts  warm  in  the  winter's  cold,  and  a  part  of  the 
fuel  may  be  wasted  as  heat.  In  both  cases  the  motion  and 
the  heat  are  derived  from  the  power  in  the  fuel.  The  casual 
observer  sees  the  moving  train,  but  the  expert  engineer  alone 
knows  how  and  why  the  wheels  go  around.  The  physiologist 
busies  himself  answering  the  similar  how  and  why  regarding 
the  mechanism  of  living  things. 

Before  taking  up  the  details  of  the  work,  we  may  copy  the 
last  general  pronouncement  of  Voit^  upon  the  subject  of  metab- 
olism.    It  reads: 

>  Voit:   "Miinchener  medizinische  Wochenschrift,"  1902,  Bd.  xlix,  p.  233. 


44  SCIENCE   OF   NUTRITION. 

"The  unknown  causes  of  metabolism  are  found  in  the  cells 
of  the  organism.  The  mass  of  these  cells  and  their  power  to 
decompose  materials  determine  the  metabolism.  It  is  abso- 
lutely proved  that  protein  fed  to  the  cells  is  the  easiest  of  all  the 
foodstuffs  to  be  destroyed,  next  carbohydrates,  and  lastly  fat. 
The  metabolism  continues  in  the  cells  until  their  power  to 
metabolize  is  exhausted.  All  kinds  of  influences  may  act  upon 
the  cells  to  modify  their  ability  to  metabolize,  some  increasing 
it  or  others  decreasing  it.  To  the  former  category  belong 
muscular  work,  cold  of  the  environment  (in  warm-blooded  ani- 
mals), abundant  food,  and  warming  the  cells.  To  the  latter, 
cooling  the  cells,  certain  poisons,  etc. 

"In  speaking  of  the  power  of  the  cells  to  metabolize,  I  have 
not  meant  thereby,  as  may  be  seen  from  all  my  writings,  that  the 
cells  must  always  use  energy  in  order  to  metabolize,  but  rather 
I  have  understood  thereby  the  sum  of  the  unknown  causes  of  the 
metabolic  ability  of  the  cells — as  one  speaks  of  the  fermentative 
'power'  of  yeast  cells. 

"The  metabolism  of  the  different  foodstuffs  varies  with  the 
quality  and  quantity  of  the  food.  Protein  alone  may  bum,  or 
little  protein  and  much  carbohydrates  and  fat.  I  have  deter- 
mined the  amount  of  the  metabolism  of  the  various  foodstuffs 
under  the  most  varied  conditions.  All  the  functions  of  metab- 
olism are  derived  from  the  processes  in  the  cells.  In  a  given 
condition  of  the  cells,  available  protein  may  be  used  exclusively 
if  enough  be  furnished  them.  If  the  power  of  the  cells  to  metab- 
olize is  not  exhausted  by  the  protein  furnished,  then  carbo- 
hydrates and  fats  are  destroyed  up  to  the  limit  of  the  ability  of 
the  cells  to  do  so. 

"From  this  use  of  materials  arise  physical  results,  such  as 
work,  heat,  and  electricity,  which  we  can  express  in  heat  units. 
This  is  the  power  derived  from  metabolism. 

"It  is  possible  to  approach  the  subject  in  the  reverse  order, 
that  is,  to  study  the  energy  production  (Kraftwechsel)  and  to 
draw  conclusions  regarding  the  metabolism  (Stoffwechsel).     It 


INTRODUCTORY.  45 

is  perfectly  possible  to  say  that  the  requirement  of  energy  in  the 
body  or  the  production  of  the  heat  necessary  to  cover  heat  loss, 
or  for  energy  to  do  work,  are  controlling  factors  of  the  metab- 
olism; since  on  cooling  the  body  or  on  working  correspond- 
ingly more  matter  is  destroyed.  But  one  must  not  conclude 
that  the  loss  of  body  heat  and  muscular  work  are  the  immediate 
causes  of  this  increased  metabolism.  The  causes  lie  in  the 
peculiar  conditions  of  the  organism,  and  muscle  work  and  loss 
of  heat  are  merely  factors  acting  favorably  upon  those  causes, 
raising  the  power  of  the  cells  to  metabolize.  In  virtue  of  this 
more  is  destroyed,  and  secondarily  the  power  to  work  and  in- 
creased heat  production  are  determined. 

"The  requirement  for  energy  cannot  possibly  be  the  cause 
of  metabolism,  any  more  than  the  requirement  for  gold  will  put 
it  into  one's  pocket.  Hence  the  production  of  energy  has  a  very 
definite  upper  limit,  which  is  afforded  by  the  ability  of  the  cells 
to  metabolize.  If  the  cells  will  metabolize  no  more,  then  fur- 
ther increase  of  work  ceases  even  in  the  presence  of  direst 
necessity;  and  this  is  also  the  case  with  the  heat  production, 
even  though  it  were  very  necessary,  and  we  were  likely  to 
freeze. * 

"I  therefore  maintain  my  'older'  point  of  view,  that  of  pure 
metabolism,  in  order  to  explain  the  phenomena  of  nutrition,  I 
am  convinced  that  it  is  the  right  way,  and  that  the  clearest 
and  most  unifying  development  will  be  possible  as  one  inves- 
tigates what  substances  are  destroyed  under  different  circum- 
stances, such  as  work,  and  loss  of  heat,  and  how  much  of  the 
different  materials  must  be  fed  to  maintain  the  body  in  con- 
dition." 


ADDENDUM  CONCERNING  THE  NATURE  OF  THE  FECES. 

In  the  historical  introduction  just  given  it  has  been  shown  that 
the  nitrogen  of  the  urine  and  feces  can  be  made  a  measure  for 
the  determination  of  protein  metabolism.     It  is  easy  to  com- 


46  SCIENCE   OF   NUTRITION. 

prehend  that  urinary  constituents,  such  as  urea,  uric  acid,  the 
purin  bases,  creatinin,  etc.,  are  derived  from  the  metabolism 
of  flesh  in  the  body,  whether  the  flesh  be  the  body's  own  or  that 
of  an  animal  fed  to  it.  But  the  intestinal  canal  where  the  feces 
are  formed  is  a  long  tube  open  at  both  ends,  through  which  may 
pass  the  nitrogen  gas  of  the  air  swallowed  and  indigestible  sub- 
stances such  as  hair,  tacks,  etc.  In  diarrhea  the  curds  of  milk, 
pieces  of  undigested  meat  or  bread,  and  large  quantities  of  fat 
are  in  evidence.  These  common  observations  would  seem  to 
justify  the  popular  supposition  that  normal  feces  are  made  up 
of  the  undigested  residues  of  the  foodstuffs.  In  truth,  however, 
this  is  very  far  from  the  fact.  -The  feces  are  chiefly  the  unab- 
sorbed  residues  of  intestinal  excretions. 

The  collection  of  the  feces  for  a  given  period  of  nutrition  is 
more  difficult  than  the  collection  of  the  urine.  The  urine  may 
be  collected  every  two  hours  and  may  fairly  represent  the  pro- 
tein metabolism  of  the  time,  but  the  feces  are  normally  passed 
but  once  a  day  by  a  man  on  a  mixed  diet,  and  only  once  in  five 
days  by  a  dog  fed  with  meat.  Furthermore,  particles  fed  to  a 
man  are  not  usually  passed  in  his  feces  for  two  or  three  days. 
The  feces  formed  during  a  certain  digestive  period  might  there- 
fore leave  the  body  two  or  three  days  after  the  urine  was  drawn 
from  the  bladder.  To  obtain  clear  results  Voit  fed  a  dog  with 
60  grams  of  bones  in  a  preliminary  diet  eighteen  hours  before 
the  regular  feeding  began.  These  bones  yielded  a  whitish 
mark  in  the  fecal  excretion.  All  feces  subsequent  to  the  mark 
were  attributed  to  the  diet  used  in  the  experiment.  At  the  con- 
clusion of  the  experiment  a  second  diet  containing  bones  was 
given.  The  whitish  excrement  formed  from  this  indicated  the 
end  of  the  feces  of  the  period.  For  the  same  purpose  Rubner^ 
gave  milk  (2  liters)  to  a  man,  the  last  portion  of  the  milk  being 
taken  eighteen  hours  before  the  commencement  of  a  period  of 
feeding.  The  milk  feces  give  a  distinct  whitish  dividing  line. 
A  teaspoonful  of  lampblack  may  also  be  readily  made  use  of 

^Rubner:   "Zeitschrift  fiir  Biologic,"  1879,  Bd.  xv,  p.  119. 


INTRODUCTORY.  47 

in  man  and  in  animals.  Cremer^  uses  freshly  precipitated  silicic 
acid  (lo  to  25  grams  mixed  with  40  to  100  grams  fat)  instead  of 
bones.  This  gives  excellent  results,  as  it  avoids  the  albuminoid 
nitrogen  in  the  bones,  and  is  of  great  advantage  if  the  calcium 
or  other  ash  constituents  of  the  feces  are  to  be  determined. 

In  the  fundamental  experiments  Voit  found  that  a  fasting 
dog  weighing  30  kilograms  excreted  1.88  grams  of  dry  fecal 
matter  per  day,  containing  0.15  gram  of  nitrogen.  Evidently 
these  starvation  feces  are  not  derived  from  the  food,  but  must  be 
derived  from  the  matter  passed  from  the  body  into  the  intestinal 
canal.  An  analogous  condition  is  found  in  the  intestinal  tract 
of  the  new-born  infant.  The  meconium  consists  principally  of 
the  unabsorbed  residues  of  the  bile,  of  glycocholic,  taurocholic, 
and  fellic  acids,  of  cholesterin  and  lecithin,  colored  by  bili- 
rubin or  biliverdin.  The  absence  both  of  putrefaction  and  the 
acid  of  the  gastric  juice  prevents  the  breaking  up  and  reabsorp- 
tion  of  many  of  these  substances,  processes  which  occur  soon 
after  birth.  The  fasting  dog  of  30  kilograms,  mentioned  above, 
excreted  1.88  grams  of  dry  feces,  but  a  fasting  dog  of  20.3 
kilograms  may  yield  4.3  grams  of  dry  bile  solids  in  twenty- 
four  hours.^  The  ordinary  starvation  feces  therefore  cannot 
consist  of  the  total  of  the  excretions  from  the  body  into 
the  digestive  tract,  but  are  rather  their  unabsorbed  re- 
mainder. 

When  meat  was  given,  Bischoff  and  Voit^  found  that  the 
production  of  feces  was  not  proportional  to  the  amount  of  meat. 
The  following  table  illustrates  the  average  amount  of  dry  feces 
produced  by  a  dog  weighing  35  kilograms  after  feeding  different 
quantities  of  meat: 

Meat  in  Gbaus.  Dry  Feces. 
500  10.7 

1800  II. 2 

2500  11-93 

'.Cremer:  Ibid.,  1897,  Bd.  xxxv,  p.  391. 

'Voit:  Ibid.,  1894,  Bd.  xxx,  p.  548. 

'Bischoff  and  Voil:   "Die  Ernahrung  des  Fleischfressers,"  i860,  p.  291. 


48  SCIENCE   OF  NUTRITION. 

The  feces  had  the  same  pitch-black  color  as  starvation  feces 
and  were  similar  to  the  2  grams  of  feces  which  would  have  been 
produced  by  the  same  dog  had  he  been  starving.  No  muscle 
fibers  and  no  protein  could  be  detected.  It  seemed  clear  that 
the  meat  feces  differed  from  the  starvation  feces  mainly  in 
quantity,  and  that  this  quantity  was  larger  because  the  secre- 
tions into  the  intestines  had  been  stimulated  by  the  passing 
food. 

Fat  ingested  with  the  meat  in  moderate  quantities  had  no 
influence  on  the  feces.  Nor  had  sugar,  unless  its  fermentation 
produced  diarrhea.  Bread  somewhat  increased  the  volume  of 
the  feces,  which  contained  some  undigested  starch.  Here  an 
irritation  of  the  intestinal  canal  by  the  bread  produced  a  larger 
excretion  into  the  intestine. 

The  source  of  the  feces  was  further  investigated  by  Hermann,^ 
whose  work  was  later  elaborated  by  Fritz  Voit.^  The  latter 
separated  a  loop  of  the  intestine  about  a  third  of  a  meter  long 
from  the  rest  of  the  intestine  of  a  starving  dog.  Both  ends  of 
the  loop  were  tied  and  the  loop  remained  in  the  abdomen  in 
connection  with  its  normal  nerve  and  blood  supply.  The  two 
ends  of  the  remaining  portion  were  reunited.  After  a  few  days 
food  could  be  given  and  the  normal  excretion  of  feces  took  place. 
After  three  weeks  the  animal  was  killed.  It  was  found  that 
the  isolated  loop  contained  a  thick,  fecal-looking  mass.  It  was 
found  that  the  dry  solids  of  this  mass  contained  the  same  per- 
centage of  nitrogen  as  did  the  feces  passed  by  the  dog  during 
the  three  weeks  of  the  experiment.  It  was  also  calculated  that 
the  amount  of  nitrogen  excreted  through  the  wall  of  the  intestinal 
loop  per  square  meter  of  its  surface  was  nearly  the  same  per 
unit  of  area  as  the  amount  of  nitrogen  in  the  feces  when  spread 
over  the  surface  of  the  whole  of  the  rest  of  the  intestine.  The 
following  table  shows  this : 

^Hermann:    "Pfliiger's  Archiv,"  1890,  Bd.  xlvi,  p.  93. 

^  F.  Voit:   "Zeitschrift  fiir  Biologic,"  1892,  Bd.  xxix,  p.  325. 


INTRODUCTORY. 


49 


Dog  I.. 
Dog  III 


Percentage  of  N 
IN  THE  Dry 

Substance. 


Grams  N  from  i  Sq. 
M.  IN  24  Hours. 


Feces. 


5.62 
5-27 


Content 
of  Loop. 


S-32 
6.88 


Feces. 


0.28 
0.25 


Content 
OF  Loop. 


0.22 
0.32 


The  loop  contained  fat  and  fatty  acids  in  greater  quantity 
than  is  normally  found  in  feces,  which  may  indicate  a  usual 
reabsorption  of  these  substances. 

Fritz  Voit  has  therefore  shown  that  the  excretion  of  sub- 
stances from  an  isolated  loop  of  the  intestine  produces  a  mass 
of  a  similar  constitution  and  of  nitrogen  output  equal  to  that 
in  the  normal  intestine  of  the  same  animal  through  which  meat 
and  fat  were  passing.  He  therefore  concludes  that  the  feces 
are  derived  principally  from  the  substances  excreted  through  the 
wall  of  the  intestine.  The  nitrogen  so  excreted  is  as  much  to 
be  considered  a  product  of  protein  metabolism  as  is  the  nitrogen 
of  urea.  It  is  regrettable  that  very  little  is  known  regarding 
the  chemistry  of  these  nitrogenous  compounds  excreted  into  the 
intestine. 

It  has  been  seen  that  the  feeding  of  simple  foodstuffs,  such 
as  meat,  fat,  and  sugar,  scarcely  influenced  the  composition  of 
the  feces  in  the  dog.  In  herbivora  we  pass  to  another  extreme. 
Here  vast  amounts  of  cellulose  are  eaten,  a  great  part  of  which  is 
never  disintegrated,  but  even  after  long  retention  in  the  capacious 
intestinal  tract  is  passed  in  the  feces.  After  giving  an  ordinary 
fodder  to  a  cow,  as  much  nitrogen  may  be  passed  in  the  feces  as 
in  the  urine.  Under  such  conditions  as  these,  the  very  volu- 
minous feces  evidently  do  consist  largely  of  the  undigested 
residues  of  the  fodder.  Armsby  and  Fries^  have  shown  that 
only  45  per  cent,  of  the  energy  contained  in  hay  is  of  actual  use 

'  ArmsVjy  and  Fries:  Bulletin  101,  1908,  Bureau  of  Animal  Industry,  U.  S. 
Dept.  of  Agriculture. 

4 


50  SCIENCE   OF  NUTRITION. 

in  cattle  feeding.  The  waste  in  the  feces  reaches  41  per  cent., 
in  the  urine  7.25,  and  in  methane  gas  6.75  per  cent,  of  the  total 
energy  content. 

Concerning  the  fecal  production  in  man,  it  has  been  found 
that  Cetti^  excreted  3.8  grams  of  dry  fecal  solids  per  day  during 
a  fast  of  ten  days,  Breithaupt  2  grams,  and  a  medical  student^ 
2.2  grams,  less  in  reality  than  would  a  dog  of  similar  size. 
Benedict^  states  that  he  was  unable  to  find  any  evidence  of  the 
formation  of  feces  during  a  seven-day  fast  in  man. 

Rieder*  gave  a  man  a  diet  containing  starch,  sugar,  and 
lard  from  which  a  cake  was  baked.  The  food  contained  no 
nitrogen,  but  the  fecal  excretion  was  0.54,  0.87,  and  0.78  gram 
of  nitrogen  per  day,  contrasting  with  0.316  gram  from  Cetti, 
0.113  from  Breithaupt,  and  0.13  from  a  medical  student  during 
fasting.  The  food,  even  though  it  contains  no  protein,  stimulates 
the  fecal  production. 

Wallace  and  Salomon^  have  administered  250  grams  of 
cane  sugar  daily  to  normal  persons  and  to  patients  suffering 
from  intestinal  diarrhea  and  have  determined  the  amount  of 
fecal  nitrogen  during  periods  of  two  or  three  days.  The  sugar 
was  given  in  doses  of  50  grams  dissolved  in  300  c.c.  of  water 
and  flavored  with  fruits,  such  as  apple  and  lemon,  or  with 
wine.     Their  results  with  this  diet  were  as  follows: 

N  IN  Feces  per  Day. 
Grams. 

Normal  man 0.539 

" 0.380 

Tuberculous  ulceration  of  intestine 3-075 

4.186 

Cancer  of  intestine i  .74 

"       "         "         1.974 

Catarrh  of  intestine  (severe) i  .464 

1.087 

^Lehmann,  Miiller,  I.  Munk,  Senator,  Zuntz:  "Virchow's  Archiv,"  1893, 
Bd.  cxxxi,  Suppl.  Heft. 

^Johansson,  Landergren,  Sonden,  Tigerstedt:  "Skandin.  Archiv  fur 
Physiologic,"  1896,  Bd.  vii,  p.  29. 

^Benedict:  "  Influence  of  Inanition  on  Metabolism,"  Carnegie  Institution, 
1907,  p.  345- 

^Rieder:    "Zeitschrift  fiir  Biologic,"  1884,  Bd.  xx,  p.  378. 

^Wallace  and  Salomon:  " Medizinische  Klinik,"  1909,  No.  16. 


INTRODUCTORY.  5 1 

It  is  evident  that  the  quantity  of  fecal  nitrogen  eliminated  in 
intestinal  diseases  is  largely  increased. 

It  has  been  stated  that  Voit  early  noticed  the  occurrence  of 
starch  particles  in  the  feces.  A  large  number  of  experiments 
have  been  made  to  test  the  digestibility  of  the  various  vegetables 
and  cereals.  Rubner^  fed  an  able-bodied  soldier  on  3078  grams 
of  variously  cooked  potatoes  daily  and  found  pieces  of  potatoes 
in  the  feces.  He  notes  that  an  inhabitant  of  Ireland  will  eat 
4500  grams  of  potatoes  a  day.  Friedrich  Miiller  writes  that 
after  feeding  a  large  quantity  of  bread,  the  feces  may  have 
practically  the  same  composition  as  bread. 

The  better  understanding  of  this  question  of  the  "digesti- 
bility" of  the  carbohydrates  has  come  through  the  work  of 
Prausnitz  ^  and  his  associates,  Moeller  and  Kermauner.  Moeller 
found  that  no  starch  appeared  in  the  feces  after  feeding  well- 
cooked  white,  rye,  and  graham  bread,  rice  or  potatoes  (even 
when  fed  in  pieces)  or  legumes  when  they  were  prepared  in  the 
form  of  puree.  Legumes  not  in  the  form  of  puree,  such  as 
string  beans  eaten  as  salad,  may  resist  the  action  of  the  digestive 
juices  so  that  the  starch  -contents  of  the  cell  are  untouched,  and 
the  vegetable  cells  appear  in  the  feces.  These  facts  explain 
the  appearance  of  bread  in  the  feces  if  the  bread  be  badly 
cooked,  or  if  such  a  "heavy"  bread  as  pumpernickel  be  eaten. 
The  imperfectly  cooked  bread  contains  starch  granules  whose 
coverings  are  impermeable  to  the  digestive  juices,  as  are  also 
many  of  those  in  the  unbolted  rye  of  pumpernickel. 

Prausnitz  finds  that  if  a  man  be  put  on  a  rice  diet  and  then 
meat  be  substituted  for  most  of  the  rice,  the  composition  of  the 
feces  does  vary  with  the  diet.  Such  feces  he  calls  normal  feces. 
They  may  contain  a  negligible  quantity  of  fibers  of  meat  (Ker- 
mauner) or  of  cellulose  from  the  rice. 

The  feces  of  six  persons  placed  alternately  on  meat  and  rice 

'Rubner:   "Zeitschrift  fiir  Biologic,"  1879,  Bd.  xv,  p.  146. 
*Fr.  Miiller:   Ibid.,  1884,  Bd.  xx,  p.  375. 
^Prausnitz:   Ibid.,  1897,  Bd.  xxxv,  p.  335. 


52 


SCIENCE    OF    NUTRITION. 


diets  yielded  normal  feces,  the  percentage  composition  of  the 
dry  solids  of  which  was  as  follows: 

COMPOSITION  OF  FECES  ON  DIFFERENT  DIETS. 


No. 

Person. 

Principal  Food. 

N%. 

Ether'  Extract 
%. 

Ash  %. 

I 

H. 

Rice 

8.S3 

12.43 

15-37 

2 

H. 

Meat 

8-75 

15.96 

14.74 

3 

M. 

Rice 

8-37 

18.23 

11.05 

4 

M. 

Meat 

9.16 

16.04 

12.22 

5 

W.  P. 

Rice 

8-59 

15.89 

12.58 

6 

W.  P. 

Meat 

8.48 

17-52 

13-13 

7 

J.  Pa. 

Rice 

8.2s 

14.47 

8 

J.  Pa. 

Meat 

8.16 

15.20 

9 

F.  Pi. 

Rice 

8.70 

16.09 

lO 

F.  Pi. 

Meat 

9-05 

15-14 

II 

Vegetarian. 

Rice 

8.78 

18.64 

12.01 

Average, 

8.65 

16.39 

13.82 

It  is  seen  from  this  that  whether  the  food  solids  contain  1.5 
per  cent.  N,  as  in  rice,  or  ten  times  that,  as  in  meat,  the  composi- 
tion of  the  feces  remains  uninfluenced.  Normal  feces  result 
from  the  eating  of  any  food  which  is  completely  digested  and 
absorbed.  In  all  such  cases  these  feces  have  the  same  composi- 
tion and  are  derived  from  the  intestinal  wall.  It  is  therefore 
not  astonishing  that  a  vegetarian  of  many  years'  standing 
produced  the  same  kind  of  feces  when  fed  on  rice  as  did  the  other 
men.  The  same  quality  of  feces  has  been  obtained  after  giving 
good  bread. 

In  this  connection  it  is  interesting  to  note  that  the  heat  value 
of  one  gram  of  human  feces  is  very  constant  whether  the  person 
is  on  a  meat  diet  or  a  medium  mixed  diet.  Rubner^  gives  the 
heat  value  of  one  gram  of  organic  matter  in  the  feces  of  a  man 
on  a  meat  diet  at  6.403  cal.,  while  on  a  mixed  diet  one  gram  varies 
between  6.061  and  6.357  cal.  The  average  fuel  value  of  feces 
is  therefore  6.2  calories  per  gram  of  dry  organic  substance,  and 
this  changes  only  when  there  is  a  poor  utilization  of  the  food.^ 

^  Rubner:   "Die  Gesetze  des  Energieverbrauchs,"  1902,  p.  35. 

^Rubner:   v.  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1903,  p.  32. 


INTRODUCTORY.  53 

According  to  Lhorisch/  one  may  calculate  the  approximate  heat 
value  of  feces  by  reckoning  the  nitrogen  therein  as  protein  nitro- 
gen and  multiplying  the  "protein,"  "fat"  and  carbohydrate 
present,  by  their  usual  heat  value.  The  sum  of  these  is  said  to 
give  a  rough  estimate  of  the  calorific  loss  through  the  feces. 

After  eating  pumpernickel,  bad  bread,  or  string  beans  the 
waste  of  undigested  residues  of  these  substances  may  appear 
in  the  feces,  changing  its  composition  and  loAvering  its  per- 
centage of  nitrogen  content. 

In  general,  Prausnitz  finds  no  difference  between  the  digesti- 
bility and  absorbability  of  animal  and  vegetable  foods.  Meat, 
rice,  and  bread  from  flour  are  all  digested' and  absorbed.  The 
ordinary  feces  indicate  whether  a  given  food  is  a  small  or  a 
great  feces  builder,  not  how  much  or  how  little  food  has  been 
used  for  the  organism. 

The  value  in  such  foods  as  cabbage,  string  beans,  cauliflower 
and  the  like  lies,  aside  from  their  flavor,  in  the  fact  that  their 
indigestible  waste  may  enhance  peristalsis  in  the  intestine. 
Their  food  value  is  small,  and  if  given  to  those  with  weak 
digestions,  is  dubious.  MendeP  points  out  that  edible  car- 
bohydrate substances,  like  Iceland  moss,  agar-agar,  Jerusalem 
artichokes,  and  inulin,  are  scarcely  attacked  by  the  digestive 
juices  and  therefore  have  little  or  no  direct  nutritive  function. 
He  ^  also  finds  that  the  proteins  of  mushrooms  are  not  digested 
in  the  organism. 

^Lhorisch:   "Zeitschrift  fiir  physiologische  Chemie,"  1904,  Bd.  xli,  p.  308. 
'Mendel:    "Zentralblatt  fiir  Stoffwechsel,"  1908,  Bd.  iii,  p.  641. 
'  Mendel:   "American  Journal  of  Physiology,"  1898,  vol.  i,  p.  225. 


CHAPTER  II. 
STARVATION. 

Nutrition  may  be  defined  as  the  sum  of  the  processes  con- 
cerned in  the  growth,  maintenance,  and  repair  of  the  hving  body- 
as  a  whole  or  of  its  constituent  organs. 

An  intelligent  basis  for  the  understanding  of  these  processes 
is  best  acquired  by  a  study  of  the  organism  when  it  is  Hving 
at  the  expense  of  materials  stored  within  itself,  as  it  does  in 
starvation. 

Starvation  or  hunger  is  the  deprivation  of  an  organism  of 
any  or  all  the  elements  necessary  to  its  nutrition.  Thus  when 
carbohydrates  and  fats  only  are  eaten,  protein  hunger  ensues. 
If  the  body  is  deprived  of  water  or  of  calcium,  thirst  or  calcium 
hunger,  as  the  case  may  be,  follows.  Complete  starvation 
occurs  when  all  the  required  elements  are  inadequate.  A  fasting 
dog  to  whom  no  food  or  drink  is  offered  does  not  undergo 
starvation  in  this  sense,  for  the  metabolized  tissue  furnishes 
enough  water  for  the  urine  and  respiration.  There  is  also  no 
water  hunger  in  a  dog  when  meat  is  ingested,,  for  the  meat 
contains  enough  water  to  dissolve  the  end-products  of  its 
metabolism  in  the  urine.  Dogs  and  cats  have  no  sweat  glands 
in  the  skin  except  in  the  pads  of  their  feet.  They  therefore 
are  not  so  susceptible  to  water  hunger  as  is  man,  whose  body 
surface  is  constantly  losing  moisture. 

A  true  picture  of  water  hunger  is  presented  by  Straub,^  who 
gave  a  dog  dry  meat  powder  mixed  with  fat.  Under  these  cir- 
cumstances water  is  withdrawn  from  the  tissues  to  dissolve  the 
urea  formed.  He  found  that  muscles  may  lose  20  per  cent,  of 
their  water  content  without  pathological  manifestations,  al- 
though withdrawal  of  water  somewhat  increased  the  protein 
metabolism.     The  experiment  could  not  be  carried  to  the  point 

^Straub:   "Zeitschrift  fiir  Biologie,"  1899,  Bd.  xxxviii,  p.  537. 
54 


STARVATION.  55 

of  death  from  thirst,  for  after  a  few  days  the  food  was  regularly 
vomited,  on  account  of  the  decreased  flow  of  the  digestive 
secretions  and  an  altered  condition  of  the  intestinal  canal.  The 
non-absorption  of  the  meat  powder  threw  the  body  on  the  re- 
sources of  its  own  tissue,  and  this  form  of  starvation,  as  has  been 
shown,  does  not  constitute  water  hunger. 

Rubner^  finds  that  starving  pigeons  die  of  thirst  in  four  to 
five  days,  while  those  allowed  only  water  live  twelve  days. 
Water  hunger  is  therefore  more  quickly  fatal  than  starvation 
when  water  is  allowed.  Under  the  usual  conditions  of  so- 
called  starvation  experiments  water  is  freely  allowed,  so  that 
water  hunger  does  not  enter  as  a  factor  into  the  following  dis- 
cussion. 

If  water  be  available,  the  organism  obtains  the  energy 
necessary  for  its  continued  existence  from  the  destruction  of  its 
ouTi  store  of  protein  and  fat.  After  a  variable  length  of  time 
the  organism  succumbs.  Exposure  to  cold  greatly  hastens  the 
end.  What  is  ordinarily  called  death  from  starvation  is  often 
really  death  from  exposure. 

Succi  has  fasted  several  times  for  thirty  days.  Dr.  Tanner, 
an  American  physician,  for  forty  days;  and  Merlatti  in  Paris 
for  fifty  days.  Succi  took  laudanum  in  considerable  quantity 
to  stay  the  pain  in  his  stomach,  while  Merlatti  took  only  water.^ 
The  effect  of  fasting  on  the  spirits  of  the  faster  varies  with  the 
individual.  Usually  there  is  a  loss  of  buoyancy  of  spirit,  a  de- 
creased desire  to  work,  and  a  decrease  in  the  actual  power  of 
working.  Succi,  however,  was  capable  of  considerable  exertion, 
such  as  walking  and  riding,  without  ill  effects.  A  dog  does  not 
manifest  the  same  depression  as  is  seen  in  man.  Dogs  may 
be  starved  several  days  before  they  are  run  in  a  hunt.  The 
longest  fast  on  record  is  that  of  Kumagawa's^  dog,  which  died  on 
the  ninety-eighth  day.  This  dog  was  reduced  in  weight  from 
17  to  5.96  kilograms,  a  loss  of  65  per  cent. 

'  Rubner:  v.  Leyden's  "Handbuch  der  Emahrungstherapie,"  1903,  p.  53. 

*Luciani:    "Das  Hungern,"  1890,  p.  28. 

^Kumagawa  and  Miura:    "Archiv  fiir  Physiologic,"  1898,  p.  431. 


56 


SCIENCE    OF    NUTRITION. 


The  day  to  day  history  of  the  starving  organism  must  now 
be  considered. 

In  the  first  days  the  amount  of  protein  metabolized  depends 
upon  the  two  factors,  the  glycogen  content  of  the  individual  and 
the  quantity  of  protein  ingested  before  the  starvation  period. 
The  influence  of  the  first  factor  was  shown  by  Prausnitz.^ 
Fifteen  individuals  (mostly  medical  students  who  were  taking 
a  course  of  instruction  in  the  laboratory)  fasted  for  sixty  hours. 
The  first  day's  urine  was  collected  beginning  after  twelve  hours 
of  fasting.  The  second  day's  urine  contained  in  twelve  cases 
more  nitrogen  than  that  of  the  first  day  of  starvation.  The 
lower  protein  destruction  on  the  first  starvation  day  must  have 
been  due  to  the  continued  use  of  sugar  from  the  glycogen  supply. 
It  is  known  that  the  combustion  of  sugar  considerably  reduces 
the  protein  metabolism,  so  the  second  day  and  not  the  first  of 
starvation  should  be  taken  as  the  basis  of  the  fasting  protein 
metabolism. 

This  influence  of  glycogen  metabolism  on  that  of  protein 
during  the  first  and  second  days  of  fasting  is  beautifully  shown 
in  experiments  by  Benedict^  (see  also  p.  65). 


INFLUENCE  OF  GLYCOGEN  METABOLISM  ON   THAT   OF  PRO- 
TEIN IN  FASTING.     WEIGHTS  IN  GRAMS. 


First  dav. 

Second  Day. 

Individual. 

Glycogen 
Metabolized. 

N 
Elimi- 
nated. 

Glycogen 
Metabolized. 

N 
Elimi- 
nated. 

Total. 

Per  Kg. 

Total. 

Per  Kg. 

S.  A.B 

S.  A.B 

S.  A.B 

H.  C.  K 

181.6 

135-3 
64.9 

165.6 
32.8 

3-15 
2.31 
1.09 
2-33 
0-59 

5-84 
10.29 
12.24 

9-39 
13-25 

29.7 
18.1 
23.1 

44-7 
41.6 

0.52 
0.31 

0-39 
0.64 
0.76 

11.04 
11.97 
12.45 
14.36 
13-53 

H.  R.  D 

It  is  evident  that  where  there  is  an  abundant  glycogen  re- 
serve the  protein  metabolism  is  reduced  by  the  oxidation  of 

^Prausnitz:  "Zeitschrift  fiir  Biologie,"  1892,  Bd.  xxix,  p.  151. 
^Bendict:  "Metabolism  in  Inanition,"  Carnegie  Institution  of  Washington, 
1907. 


STARVATION, 


57 


carbohydrates,  but  where  there  is  little  glycogen  to  draw  upon 
the  protein  metabolism  is  high  even  on  the  first  day  of  starvation. 
The  second  factor,  or  the  influence  of  the  previous  meat  in- 
gestion, is  especially  dominant  in  dogs.  Voit  ^  fed  a  dog  weigh- 
ing 35  kg.  with  different  quantities  of  meat  and  noticed  the 
effect  on  urea  elimination  during  subsequent  starvation.  The 
results  were  as  follows: 

INFLUENCE   OF  PREVIOUS   DIET   ON   UREA   ELIMINATION   IN 
STARVATION. 


Grams 

OF  Urea  Excreted  During  Starvation 
Following  Various  Diets. 

Meat, 
2500  G. 

Meat, 

1800  G.; 

Fat,  250  G. 

Meat, 
1500  G. 

Meat, 
1500  G. 

Bread. 

Last  food  day 

180.8 
60.1 
24.9 
19.1 

17-3 
12.3 

^3-3 
12.5 
10. 1 

130.0 
37-S 
23-3 
16.7 
14.8 
12.6 
12.8 
12.0 

1 10.8 
29.7 
18.2 

17-5 
14.9 
14.2 
13.0 
12. 1 
12.9 

110.8 
26.5 
18.6 

15-7 
14.9 
14.8 
12.8 
12.9 
12. 1 
11.9 
11.4 

24.7 
19.6 

15-6 
14.9 
13.2 
12.7 
13.0 

ist  fasting  day  

2d         "         "     

5d        "         "     

4th       "         "     

5th       "         "     

6th       "         "     

7th       "         "     

8th       "         "     

Qth        "          "     

loth      "         "     

It  is  evident  from  this  that  on  the  sixth  day  of  starvation  the 
urea  elimination  was  the  same  in  all  cases,  or  about  thirteen 
grams  of  urea  per  day.  He  deducted  the  twelve  grams  from 
what  he  had  found  for  the  first  days  and  obtained  the  grams  of 
urea  which  were  derived  from  the  previous  food,  as  follows : 


UREA     ELIMINATION 


IN     STARVATION 
PREVIOUS  DIET. 


ATTRIBUTABLE     TO 


(Last  food  day) 
1st  fasting  day 
2d 

3<i 

4th       " 

5th       " 


Meat, 

Meat, 

Meat, 

Meat. 

1500  G. 

1800  G; 
Fat,  2  so  G. 

(118.0) 

1500  G. 

1500  G. 

(168.8) 

(98.8) 

(98.8) 

48.1 

25-5 

17.7 

14-5 

12.9 

"•3 

6.2 

6.6 

7-1 

4-7 

5-5 

3-7 

5-3 

2.8 

2.9 

2.9 

0.3 

0.6 

2.2 

2.8 

Bread. 

(12.7) 
7.6 
3-6 
2.9 
1.2 
0.7 


Voit:   "Zeitschrift  fur  Biologic,"  1866,  Bd.  ii,  p.  307. 


58  SCIENCE    OF   NUTRITION. 

The  amount  of  extra  protein  metabolism  is  seen  from  the 
above  to  be  directly  dependent  on  the  previous  feeding,  a  com- 
mon level  being  reached  in  all  cases  on  the  fifth  day  of  fasting. 

These  experiments  led  Voit  to  differentiate  between  "cir- 
culating protein,"  which  could  be  absorbed,  carried  to  the 
tissues,  and  burned,  and  "organized  protein,"  the  more  re- 
sistant living  protein  of  the  tissues  themselves.  Voit^  stated 
that  in  metabolism  the  lifeless  protein  furnished  to  the  cells  by 
the  blood  was  used  in  preference  to  the  living  organized  tissue 
protein.  He  quoted  Landois's  experiments,  which  show  that 
after  producing  an  artificial  plethora  through  injection  of  blood, 
the  serum  proteins  are  readily  burned  and  their  nitrogen  elim- 
inated in  the  urine,  while  the  red  blood-cells  containing  the 
organized  protein  are  only  slowly  destroyed.  If  serum  alone 
be  transfused,  its  protein  is  rapidly  destroyed.^ 

Even  in  starvation  there  is  evidence  of  "circulating  protein" 
as  food  for  the  tissues.  Thus  Miescher  showed  that  the  salmon, 
after  entering  the  Rhine  from  the  sea,  virtually  starves.  Yet 
the  genital  organs  of  both  male  and  female  develop  greatly, 
this  being  at  the  expense  of  the  muscles,  which  may  lose  55  per 
cent,  of  their  weight.  This  protein  must  have  been  carried  to 
the  various  parts  of  the  body  in  the  circulating  blood-stream. 
Miescher  finds  no  indication  of  any  destruction  of  muscle  fibers 
in  this  process  of  emaciation.  It  is  interesting  in  this  con- 
nection to  note  that  A.  R.  MandeP  has  been  able  at  a  pressure 
of  300  to  350  atmospheres  acting  on  lean  meat  seventy- two 
hours  old  to  press  out  a  fluid  containing  44  per  cent,  of  the  pro- 
tein present  in  the  fibers,  and  this  without  visible  change  from  the 
normal  histological  appearance  of  the  muscle. 

It  seems  quite  possible  that  in  ordinary  starvation  protein 
from  muscle  and  other  tissues  passes  to  the  blood  and  is  carried 
to  all  the  organs  as  circulating  protein  for  the  nutrition  of  their 
cells. 

'Voit:   "Handbuch  der  Ernahrung,"  1882,  p.  300. 

^Forster:    "Zeitschrift  fiir  Biologic,"   1875,  Bd,  xi,  p.  496. 

^  Mandel :  Unpublished  work  from  the  Munich  Clinic  of  Prof.  Fr.  Miiller. 


STARVATION.  59 

The  great  work  of  Emil  Fischer  has  taught  that  the  essential 
composition  of  protein  is  a  structure  formed  of  chains  of  amino- 
acids.  He  has  constructed  artificial  pepHds,  bodies  in  which 
two  or  more  amino-acids  are  imited  together.  For  example 
glycvl-glycin  is  formed  by  the  union  of  two  molecules  of  glycocoll 
with  the  loss  of  water,  as  follows : 

HjNCHoCOOH  HJ^CHjjCO 

— H,0  =  "  I 

H^NXHjCOOH  HNCH^COOH 

Glycocoll  Glycyl-glycin. 

Fischer  has  recently  hung  together  eighteen  of  these  radicles 
in  an  octodecapeptid  containing  four  leucin  and  fourteen  glyco- 
coll molecules  and  being  1-leucyl-triglycyl-l-leucyl-triglycyl-l- 
leucyl-octoglycyl-glycin. 

J^^^XcHCHzCHNHjCO  1-leucyl 

CHjNHCO 

/ 
CHoNHCO  tri-glycyl 

'    / 
CHjNHCO 

^S'^CHCHjCH  NHCO  1-leucyl 

CHjNHCO 

/ 
CHjNHCO  tri-glycvl 

/ 
CH2NHCO 

^JlaNcHCHjCH  NHCO  1-leucyl 

CH2NHCO 

/ 
CH2NHCO 

/ 
CH2NHCO 

/ 
CHjNHCO  octo-glycyl 

/ 
CHjNHCO 

/ 
CHjNHCO 

/ 
CHjNHCO 

/ 
CHjNHCO 

CH  NHCOOH  glycin 

N  =  20.8  % 


6o  SCIENCE    OF   NUTRITION. 

This  forms  a  body  akin  to  peptone.  The  high  molecular 
complex  called  protein,  which  constitutes  the  basis  of  our  being, 
is,  after  all,  separable  into  simple  chemical  compounds.  In  the 
larger  molecule  these  amino-acids  are  chained  together,  even 
as  in  structural  framework  various  iron  beams  are  riveted 
together.  Digestive  proteolysis  or  internal  metabolism  rends 
the  higher  structure  of  the  molecule  and  leaves  its  individual 
supports,  the  amino-acids,  open  for  further  disintegration.^ 

In  modem  critical  consideration  of  the  "circulating  protein" 
it  must  be  borne  in  mind  that  the  amino-products  resulting 
from  protein  digestion  are  probably  largely  metabolized  as  such, 
and  are  only  in  part  regenerated  into  protein  within  the  organ- 
ism (page  1 88).  Since  the  composition  of  the  blood-plasma  is 
practically  the  same  in  starvation  as  after  large  digestion  of  meat 
(page  78),  it  is  evident  that  the  storage  of  such  regenerated 
protein  must  be  effected  elsewhere  than  in  the  blood  (page  186). 

Another  thought  is  that  when  tissue  protein  becomes  "  cir- 
culating protein"  in  the  cited  case  of  the  salmon,  modem  theory 
would  assume  its  cleavage  into  amino-acids  previous  to  its 
regeneration  into  the  tissue  protein  of  the  genital  organs.  Thus 
KosseP  estimates  that  a  salmon  weighing  9  kg.  deposits  at 
breeding-time  in  his  testicles  27  grams  of  salmin  containing 
22.8  grams  of  arginin.  Kossel  calculates  that  metabolism  of 
muscle  protein  during  this  time  yields  ample  arginin  to  form 
the  new  salmin. 

Although  Voit's  term  "circulating  protein,"  has  been  fre- 
quently misunderstood  and  differently  construed,  yet  discussion 
of  the  subject  has  served  to  emphasize  the  distinction  between 
the  behavior  of  living  tissue  protein  and  the  lifeless  protein 
(or  proteolytic  cleavage  products)  of  the  nourishing  fluid. 

This  point  is  furthermore  well  illustrated  by  the  behavior 
of  gelatin.     Voit  has  demonstrated  that  although  gelatin  can 

^  For  further  details  see  Plimmer:  "  The  Chemical  Constitution  of  the 
Proteins,"  1908. 

^Kossel:   "Biochemisches  Centralblatt,"  1906,  Bd.  v,  p.  33. 


STARVATION. 


6i 


never  be  converted  into  tissue  protein  nor  be  retained  in  the 
body,  its  ingestion  may  in  part  prevent  the  combustion  of  the 
living  protein  tissue  of  the  body  (page  iii). 

The  amount  of  protein  metabolized  by  a  starving  animal  in 
good  condition  bears  quite  a  constant  relationship  to  the  total 
metabolism  involved.  Even  in  different  animals  this  constancy 
is  observed.  E.  Voit^  calls  attention  to  the  fact  that  the  nitrogen 
elimination  is  not  dependent  on  the  weight  of  the  animal,  since 
a  pig  of  115  kilos  produces  0.06  gram  per  kilo,  whereas  a  guinea- 
pig  weighing  but  0.6  kilo  eliminates  0.65  gram  of  nitrogen  per 
kilo,  or  ten  times  as  much.  However,  a  comparison  of  the  per- 
centage of  the  total  energy  derived  from  protein  in  fasting 
animals  in  good  condition  (i.  e.,  with  considerable  fat)  varies 
within  much  narrower  limits — between  7.3  and  16.5  per  cent. 
This  is  shown  in  the  following  table: 


NITROGEN  METABOLISM  OF  DIFFERENT  ANIMALS  IN 
STARVATION. 


Animal. 


N  Elimination. 


Weight  in 
Kg. 


Total. 


Per  Kg. 


Per  Sq.  M. 
Surface. 


Percentage 
OF  Calories 
FROM  Pro- 
tein. 


Pig 

Man 

DogI 

Dog  II  ... . 
Dog  III... 

Rabbit 

Goose 

Fowl 

Guinea-pig 


115.0 

6,S-7 
28.6 
18.7 

7.2 
2.7 

3-3 
2.1 
0.6 


6.8 
12.6 

5-1 
3-8 
2.2 
1.2 
0.8 
0.7 
0.4 


0.06 
0.20 
0.18 
0.20 
0.30 
0.46 
0.23 

0.34 
0.65 


3-2 
6.4 

5-2 

4.6 

5-2 

4.8 

3-3 
4.2 
4.2 


7-3 
15-6 
13.2 
10.7 
13-5 
16.S 

7-4 
10. o 
ip.8 


It  is  evident  from  the  above  that  an  average  of  90  per  cent, 
of  the  energy  of  the  fasting  metabolism  may  be  supplied  by 
non-protein  material.    This  material  is  fat  (see  page  26). 

If  a  fasting  organism  be  kept  at  the  same  temperature  and 
under  the  .same  conditions  a.s  regards  the  performance  of  external 
work,  the  metabolism- is  remarkably  even  from  day  to  day. 

'  E.  Voit:   "Zcitschrifl  fiir  Biologic,"  1901,  Bd.  xli,  p.  188. 


62  SCIENCE    OF   NUTRITION. 

Hanriot  and  Richet^  showed  the  even  absorption  of  oxygen 
and  elimination  of  carbon  dioxid  during  the  early  days  of  fasting 
in  man,  as  is  illustrated  in  this  table : 

Liters  O2  Liters  CO2 

PER  Hour.    •       per  Hour. 

After  17  hours' fast  17.4  15.3 

"     24       "         "  16.85  14-15 

"     2g       "         "  16.05  14-3 

"     46       "         "  16.9  14.3s 

Later  Lehmann  and  Zuntz^  made  some  experiments  on  the 
professional  faster  Cetti.  They  analyzed  his  urine  and  feces, 
and  also  obtained  two  samples  of  the  carbon  dioxid  eliminated 
between  lo  and  ii  a,  m.,  each  period  of  collection  lasting  from 
ten  to  fourteen  minutes.  In  other  words,  the  carbon  dioxid  out- 
put was  determined  for  only  twenty  to  twenty-six  minutes  daily. 
From  these  data  the  total  day's  metabolism  was  calculated. 
This  apparatus  as  used  by  Zuntz  has  the  advantage  that  it  can 
be  made  in  portable  form,  and  may  be  carried  on  the  back  in 
mountaineering.  The  person  inspires  through  a  mouth-piece 
provided  with  a  plate  of  hard  rubber  which  fits  between  the 
lips  and  the  teeth.  The  nostrils  are  closed  with  a  clamp.  The 
inspired  air  is  drawn  through  a  valve  and  the  expired  air  is 
forced  through  another  valve  to  a  gas  meter.  Arrangements  are 
also  provided  for  the  gas  analysis  of  portions  of  the  expired  air.' 
Trustworthy  results  are  obtained  only  when  the  person  under 
investigation  is  accustomed  to  the  apparatus.  It  is  of  especial 
value  when  pronounced  temporary  variations  in  the  metabolism 
are  to  be  measured.  The  method  is  only  approximately  correct, 
but  it  is  more  accurate  in  the  even  metabolism  of  starvation  than 
after  foods  have  been  ingested.  In  this  method  the  lower 
metabolism  during  the  night  is  not  taken  into  consideration. 

The  investigation  of  the  metabolism  of  Cetti  during  a  ten 
days'  fast  was  as  follows. 

^Hanriot  et  Richet:  "Comptes  rendus  de  I'Academie  des  Sciences,"  1888, 
Tome  cvi,  p.  496. 

2 Lehmann  and  Zuntz:  "Arch.  f.  pathol.  Anat.,"  1893,  vol.  cxxxi  Suppl.^ 
p.  23. 


STARVATION.  63 

METABOLISM  OF   CETTI  IN  STARVATION. 


Fasting 

Days. 

Protein. 

1 

I  to  4- 
5  to  6. 
7  to  8. 
9  to. 10 

85.88 
69.58 
66.30 
67.96 

Fat. 


136.72 

149-35 
132-38 


Calories 

from 
Protein. 


Calories 
FROM  Fat. 


329.8 

267.3 

254-7 
261. 1 


1288.2 

1237.4 

1407-3 
1247.4 


Calories, 
Total. 


1618 

1504 
1662 
1508 


Calories 
per  Kxlo. 


29.00 
28.3S 

31-74 
29.26 


A  very  careful  experiment  on  the  metabolism  of  a  fasting 
medical  student  twenty-six  years  old  was  made  by  Johansson, 
Landergren,  Sonden,  and  Tigerstedt.^  The  man  fasted  five 
days,  doing  light  work  in  the  respiration  apparatus.  The  metab- 
olism during  these  days  was  determined.  The  excreta  in  grams 
were  as  follows: 

METABOLISM  OF  J.  A.  IN  STARVATION. 


Day  op 

N  Elimination. 

C  Elimination. 

Fasting. 

Urine. 

Feces. 

Total. 

Urine. 

Feces. 

Respiration. 

Total. 

I 

2 

3 

4 

5 

12.04 
12.72 
13.48 
13-56 
11-34 

0.13 
0.13 
0.13 
0.13 
0.13 

12.17 
12.84 
13.61 
13.69 
11.47 

8.0 

8.3 

9.9 

10.3 

9-3 

188.5 
179.4 
172.2 
169.4 
165.8 

197.6 
188.8 
183.2 
180.8 
176.2 

The  evenness  of  the  carbon  and  nitrogen  elimination  is 
remarkable.  From  the  above  figures  the  following  table  of 
the  general  metabolism  is  made: 


Day  op  Fasting. 

Protein. 

Fat. 

Calories 

from 
Protein. 

Calories 

FROM 

Fat. 

Calories, 
Total. 

I 

76.1 
80.3 
85.1 
85.6 
71.7 

206.1 
191. 6 
181  2 
177.6 
181. 2 

303-5 
320.5 
339-4 
341-4 
286.1 

1916.9 
1 781. 9 
1684.7 
1651.9 
1684.7 

2220.4 

2 

2102.4 

1 

2024.1 

A. 

1992.3 

5 

1970.8 

"'Skandln.  Archiv  fur  Physiologic,"  1896,  Bd.  vii,  p.  54. 


64  SCIENCE   OF  NUTRITION. 

Further  calculation  shows  the  following  relations  between 
the  weight  of  the  individual  and  the  calorific  production: 

Day  of  Weight  Calories 

Fasting.  in  Kilos.  per  Kilo. 

1 66.99  33-15 

2 65.71  32.00 

3 64.88  31.20 

4 63.99  3^-^3 

5 63.13  31.23 

On  the  fifth  day  of  fasting  it  is  seen  that  the  individual 
oxidized  71.7  grams  of  protein,  18 1.2  grams  of  fat,  and  produced 
1971  calories,  or  31.23  calories  per  kilogram  of  body  substance. 
This  is  presumably  the  minimum  compatible  with  ordinary  life. 

Reference  has  already  been  made  to  the  notable  work  of 
Benedict  (see  p.  56)  entitled  "Metabolism  in  Inanition."  Here 
in  seventeen  experiments  on  seven  men  the  metabolism  was 
determined  during  a  fast  of  two  days,  and  in  one  instance  the 
starvation  period  extended  over  seven  days.  In  these  experi- 
ments the  metabolism  of  glycogen  was  for  the  first  time  deter- 
mined. Benedict's  fasting  individuals  were  placed  in  a  respira- 
tion calorimeter,  and  in  addition  to  the  usual  routine  the  amount 
of  oxygen  consumed  by  them  was  measured.  Knowing  the  last 
factor  Benedict  was  able  to  calculate  the  amount  of  glycogen 
destroyed  by  deducting  from  the  total  oxygen  intake  the  part 
necessary  to  oxidize  the  protein  catabolized,  and  then,  in  the 
light  of  the  knowledge  of  the  respiratory  quotient  (see  p.  28), 
apportioning  the  remainder  of  the  oxygen  to  the  non-protein 
carbon  dioxid  eliminated,  in  such  a  way  as  to  indicate  the 
amounts  of  glycogen  and  fat  destroyed.  The  heat  value  of  the 
metabolism  thus  calculated  agreed  with  the  heat  as  actually 
measured  by  the  calorimeter  in  which  the  man  lived  within  one 
half  of  one  per  cent.,  whereas  if  the  non-protein  carbon  of  the 
first  day  had  been  reckoned  as  fat  metabolized,  as  had  hereto- 
fore been  the  custom,  the  discrepancy  would  have  been  as  high 
as  five  per  cent,  in  some  instances.  This  shows  the  usefulness 
of  a  comparison  of  direct  and  indirect  calorimetry.     (See  p.  42.) 


STARVATION. 


65 


The  results  of  Benedict's  experiment  on  an  individual  who 
fasted  for  seven  days  are  here  reproduced. 

METABOLISM  OF  S.  A.  B.  DURING  A  SEVEN-DAY  FAST. 


Grams. 

Calories. 

R.  Q. 

Urine. 

Day. 

Pro- 
tein. 

Fat. 

Calcu-  Direct- 
Glyco-   lated     ly  De- 
gen.         FROM        TERM- 

Metab.    ined. 

Per 
Kg. 

Per 
Sq. 
M. 

Ratio 
N:S. 

Ratio 
NiPjOe 

1 73-4 

2 :  74-7 

3 t  78-1 

4 69.8 

5 1  65.2 

6 !  64.4 

7 60.8 

126.4 
147-5 
153-0 
144-7 
144.7 
129.8 
132-5 

64.9 
23.1 

5-4 

25-2 

8.2 

21.7 
18.7 

1796 
1790 
1785 
1734 
1636 

1547 
1546 

1765 
1768 
1797 

1775 
1649 

1553 
1568 

29.7 
29.9 
30.8 
30.8 
29.0 

27-5 
28.0 

941 
946 
969 
966 

985 
856 
869 

.78 
•75 
•74 
•75 
•74 
•75 
■74 

19.6 

18.6 

17-38 

16  II 

16.26 

16.27 

16.28 

8.55 
5-55 
6.34 
4-83 
5-23 
5-19 
4.87 

This  complete  and  recent  experiment  reafiirms  the  princi- 
ples which  have  already  been  enunciated.  Benedict  found  that 
the  pulse-rate  showed  a  distinct  tendency  to  fall.  In  the  above 
individual  the  average  pulse- rate  was  57  on  the  first  fasting  day 
and  51  on  the  seventh  day. 

E.  Voit^  gives  the  following  summary  of  the  energy  re- 
quirements during  the  early  days  of  starvation  in  man : 


GENERAL  TABLE  OF  STARVATION  METABOLISM  IN  MAN. 


Weight. 

Eneegy  in  Calories. 

OF  Fast. 

Total. 

Per  Kg. 

Per  Sq.  M. 
Surface 

Author. 

I 

I 

I  to  5 

I 

I  to  2 

- 
70.6 

70.4 
64-9 
59-5 
56.0 

2359 
2222 
2071 
1893 
1773 

33-4 
31-6 
31-9 
31-8 
31-7 

III2 

1060 

1042 

1012 

985 

Pettenkofer  and  Voit. 

Pettenkofer  and  Voit. 

Tigerstedt. 

Zuntz  and  Lchmann. 

Zuntz  and  Lehmann. 

To  this  may  be  added  the  average  results  of  the  many  ex- 
periments by  Benedict: 

'  Voit,  E.:  "Zcitschrift  fiir  Biologic,"  1901,  Bd.  xli,  p.  114. 


66  SCIENCE    OF   NUTRITION. 

METABOLISM  IN  THE  EARLY  DAYS  OF  STARVATION. 

1ST  Day.    2D  Day.  3D  Day.    4th  Day.    sth  Day. 

No.  of  experiments 18  17  9  5  2 

Average  cal.  per  kg 30.7         31.8  31.0         29.6  28.5 

"surfa^} 992        1028  991  938  88s 

This  minimal  metabolism  requirement  of  the  fasting  organ- 
ism appears  remarkably  constant  in  different  men.  Not  only 
is  the  total  metabolism  the  same  but  also  the  amounts  of  protein 
and  fat  which  yield  the  energy  are  the  same.  This  is  shown  by 
comparing  the  nitrogen  excretion  of  the  different  fasters  during 
the  first  days  of  fasting.     These  are  as  follows : 

Cetti.i    Breithaupt.2   Stjcci.3  J.A.*  Succi.5 

1 13-55  10.01  13-81  12.17  17.00 

2 12.59  9-92  11-03  '12.85  11.20 

3 13-12  13.29  13.86  13.61  10.55 

4 12.39  12.78  12.80  13-69  10.80 

5 10.70  10.95  12.84  11-47  II. 19 

6 10.10  9.88  10.12  II. 01 

It  is  thus  evident  that  if  the  organism  has  previously  been  well 
nourished,  the  fasting  metabolism  is  remarkably  even,  about 
13  per  cent,  of  the  total  energy  being  derived  from  protein  and 
87  per  cent,  from  fat. 

During  prolonged  fasting  the  nitrogen  output  sinks  much 
below  the  figures  of  the  earlier  days.  Thus  a  woman  twenty- 
four  years  old  averaged  4.15  gm.  from  the  thirteenth  to  the 
twenty-fifth  day  of  fasting.^  A  girl  nineteen  years  old  whose 
esophagus  had  been  occluded  by  drinking  sulphuric  acid  ex- 
creted 2.8  grams  of  nitrogen  on  the  sixteenth  day  of  fasting.'' 
An  invalid  of  Tuczec's^  averaged  4.25  grams  of  nitrogen  between 
the  fifteenth  and  twenty-first  days.     Under  Luciani's  obser- 

^  Munk:   "Arch.  f.  Path.,  Anat."  1893,  Bd.  cxxxi,  Suppl.  p.  25. 
i'Munk:   Ihid.,  p.  68. 
^Luciani:    "Das  Hungern,"  1890. 

*  Johansson,  Landergren,  Sonden,  and  Tigerstedt:  "Skandin.  Archiv.  fiir 
Physiol.,"  1896,  Bd.  vii,  p.  54. 

^E.  and  O.  Freund:   "Wiener  klinische  Rundschau,"  1901,  Bd.  xv,  p.  91. 
^  Seegen:  "Wiener  Acad.  Sitz.  Ber.,"  Bd.  xxxiii,  2  Abth. 
'Schultzen:   "Archiv  fiir  Physiologie,"  1863,  p.  31. 
^Tuczec:   "Arch,  fiir  Psychiatric,"  Bd.  xv,  p.  764. 


STARVATION. 


67 


vation,  Succi  excreted  4.08  grams  on  the  twenty-ninth  day,  and 
under  E.  and  O.  Freund  his  nitrogen  excretion  was  2.82  grams 
on  the  twenty-first  day.  The  latter  authors  say  that  after  this 
there  was  a  sudden  rise  in  the  amount  of  nitrogen  and  chlorin 
in  the  urine,  suggesting  the  so-called  premortal  rise,  which  caused 
them  to  stop  the  experiment.  About  3  grams  of  nitrogen 
in  the  urine  or  a  daily  destruction  of  18.75  grams  of  protein 
would  seem  to  be  the  lowest  extreme  of  protein  metabolism  in 
the  emaciated  organism  after  a  prolonged  fast.  The  analyses 
by  E.  and  O.  Freund  of  Succi's  urine  during  a  fast  of  twenty-one 
days  is  the  most  complete  record  of  the  sort.  The  daily  nitrogen 
excretion  is  ofiven  in  grams  below: 


DAILY  NITROGEN  EXCRETION  OF  SUCCI  IN  STARVATION. 


Day. 


N.      Day. 


I 
2 

3 
4 
5 
6 


N.      Day. 


17-0      » 9-74 

II. 2   '   9 10.05 

10.5510 7-12 

10.8  ,11 6.23 

II. 19  12 6. 84 

ii.oi'iS 5-14 

8.79|i4 4.66 


15 5 

16 4, 

17 5 

18 3 

19 5 

20 3. 


The  nitrogen  and  total  sulphur  ran  together  in  the  urine 
in  the  proportion  of  17.3  N  :  i  S.  Munk  found  the  relation 
s  to  be  14.7  in  Breithaupt  and  15. i  in  Cetti,  and  Benedict 
(see  p.  65)  found  16.27  during  the  fifth,  sixth,  and  seventh 
days  of  starvation.  A  similar  relation  between  N  and  S  is 
found  in  muscle.  The  sulphur  is  believed  to  be  derived  ex- 
clusively from  the  breaking  down  of  protein. 

The  nitrogen  and  total  phosphoric  acid  (PjOj)  in  the  urine 
are  not  found  in  the  same  relation  as  that  in  which  they  exist  in 
meat  (7.6  :  i),  but  there  is  a  greater  phosphoric  acid  excretion. 
This  is  also  true  of  the  calcium  excretion.  This  greater  excre- 
tion is  due  to  the  metabolism  of  the  bones  (Munk).  E.  and  O. 
Freund  found  that  the  ,;,j  fell  from  5.7  on  the  first  day  of  Succi's 


68 


SCIENCE    OF   NUTRITION. 


Starvation  to  between  4.2  and  4.4  during  the  subsequent  periods. 
Munk  found  this  value  to  be  4.4  in  Cetti  during  ten  days  and 
5.1  in  Breithaupt  during  six  days  (consult  table  on  p.  65). 

A  partial  record  of  the  work  of  E.  and  O.  Freund  on  Succi  is 
given  below.  Their  analyses  of  the  urine  of  the  first,  third,  elev- 
enth, and  twenty-first  days  of  starvation  are  in  part  reproduced. 

COMPLETE  URINARY  ANALYSIS   OF  SUCCI  ON  FIRST,   THIRD, 
ELEVENTH,  AND  TWENTY-FIRST  STARVATION  DAYS. 


Day  of  Fasting. 

1ST. 

3D- 

IITH. 

2 1  ST. 

Amt.  urine,  c.c 

1435 

17.0 

14.8 
0.29 
0.13 
0.134 

0-43 
3-2 
2.98 
14.9 
0.25 
0-33 

575 
10-55 
9-65 
0.20 
0.064 
0.198 
0.144 

1-3 

2.52 
2.56 

■378 

6.32 

5-64 
0-075 
0.042 
0-372 

o'.s' 
0.41 

i-Si 
0.31 

235 

2.82 

Total  N,  grams 

Urea  N,  grams 

1.65 

0.046 

0.034 

0.025 

O.IO 

Uric  acid  N 

Purin  base  N ...... 

Creatinin  N 

Ammonia  N 

Total  S 

Total  PjOg 

0.64 

CI 

0.7 

Ca 

Mg 

Examination  of  the  above  will  show  that  whereas  in  the 
earlier  days  of  the  experiment  the  relationship  between  urea 
nitrogen  and  total  nitrogen  is  the  normal  of  about  85  per  cent., 
during  the  last  days  it  has  fallen  to  54  per  cent.  The  balance 
of  the  total  nitrogen  not  enumerated  above  is  made  up  of 
constituents  of  unknown  character.  The  Freunds  attribute 
great  significance  to  this  distribution  of  nitrogen  in  the  urine, 
which  was  noteworthy  between  the  sixteenth  and  the  twenty- 
first  days.  A  similar  ratio  may  exist  in  the  urine  of  a  man 
unaccustomed  to  exercise  who  does  hard  work.^ 

The  relative  ammonia  excretion  was  apparently  the  same 
as  normal.  The  purin  bodies  ran  low.  The  chlorin  ex- 
cretion almost  vanished,  so  great  is  the  retentive  power  of  the 
body  for  its  sodium  chlorid  constituents.  Of  pathological 
substances,  the  urine  contained  acetone,  diacetic  acid,  urobilin, 

^Jackson:   "Archives  italiennes  de  Biologie,"  1901,  Tome  xxxvi,  p.  463. 


STARVATION.  gg 

and  dextrose.     The  dextrose  was  too  small  in  amount  to  be 
quantitatively  determined. 

Of  similar  import  is  the  experiment  by  Cathcart'  on  a  pro- 
fessional faster,  thirty-one  years  old,  a  partial  record  of  which 
is  here  presented. 

URINARY  ANALYSIS  OF  VICTOR  BEAUTE  ON  THE  FIRST  THIRD 

TWELFTH,  AND  FOURTEENTH  DAYS  OF  FASTING 

\VEIGHT  IN  GRAMS. 


Day  of  Fasting. 


Total  N 

^'rea  N 's'^S 

Ammonia  N 

Uric  acid  N 

Purin  base  N 

Creatinin  N 

Creatin  N 

Totals 

Total  P^Oj 

CI 

Ca 

Mg ::::::::: 

K 

Na 


10.51 


0.40 

0.12 

0.029 

0.42 

0.02 

0.614 

2.26 

3-2 


1372 
12.26 

0.73 
0.06 
0.032 

0-34 
0.09 
o.Sor 
2.98 

1-5 

0.216 

0.131 

^■33 
0.865 


8.77 

6.62 

1.05 

0.17 

0.023 

0.30 

0.09 

0-577 

1-55 

0.18 


7.78 
5-99 
0-73 
0.17 

0.24 
o.io 
0-536 

1-25 

0.24 

0.096 

0.037 

0-515 
0.096 


In  this  experiment  the  ammonia  excretion  rose  to  meet  an 
accompanying  acidosis.  The  creatinin  excretion  gradually 
fell,  whereas  the  creatin  excretion,  which  is  generally  considered 
an  index  of  muscle  breakdown  (see  p.  140),  remained  quite  con- 
stant. The  relation  between  the  nitrogen  and  sulphur  elimina- 
tion averaged  15  N  :  i  S,  or  similar  to  the  relation  found  in 
muscle,  which  is  14  N  :  i  S.  The  relatively  large  potassium 
excretion  and  the  small  sodium  excretion  indicated  respectively 
the  destruction  of  body  tissues  which  are  all  rich  in  potassium 
salts  and  the  conser\'ation  of  the  body's  sodium  chlorid  supply. 

A  communication  by  Brugsch  =^  shows  that  the  quantities 
of  ,9-oxybutyric  acid  and  acetone  in  the  urine  become  very  great 
in  extreme  hunger.     The  experiment  was  also  on  Succi,  be- 

'Cathcart:   "  Biochemische  Zcitschrift,"  1907,  Bd.  vi,  p.  109. 

'  Brugsch:  "Zcitschrift  fur  ex.  Pathologic  und  Thcrapie,"  1905,  Bd.  i,  j).  419. 


70 


SCIENCE    OF   NUTRITION. 


tween  the  twenty-third  and  the  thirtieth  days  of  starvation,  and 
showed  the  following  remarkable  values: 

ACETONURIA  IN  STARVATION  (SUCCI). 


Starvation  Day. 


N  IN  Grams. 


/3-oxybutyric 
Acid  in  Grams. 


Acetone  in 
Grams. 


23d.. 
24th. 
25th. 
26th. 
27th. 
28th. 
29th. 
30th. 


5-87 
6.41 
6.27 
6.18 
6.30 

4-43 
4.19 
8.42 


9.24 
8.43 
9-85 
5.28 
11.62 
6.99 

9-15 
13.60 


0.569 
0.410 
0.463 
0.569 
0.525 
0-339 
0.242 
0.115 


The  excretion  of  urea  nitrogen  ran  between  54  and  70  per 
cent.,  and  the  ammonia  nitrogen  between  15.4  and  35.3  per 
cent,  of  the  total  nitrogen  in  the  urine.  The  high  ammonia 
neutralized  the  very  considerable  acidosis. 

Albumin  is  also  of  frequent  occurrence  in  the  starvation 
urine  of  man  and  animals. 

It  has  already  been  set  forth  that  the  general  metabolism  is 
extremely  even  in  fasting,  and  it  may  be  added  that  existing 
evidence  shows  that  the  intermediary  metabolism  has  a  similar 
character.  Thus  Stiles  and  Lusk^  found  in  a  fasting  dog  made 
diabetic  with  phlorhizin  that  whereas  the  quantity  of  nitrogen 
and  sugar  eliminated  slowly  fell,  the  relation  between  the  two 
(the  Dextrose  :  Nitrogen  or  D  :  N  ratio)  remained  constant. 
This  is  shown  in  the  following  table: 

CONSTANT  RATIO  BETWEEN  DEXTROSE  PRODUCTION  AND  N 
ELIMINATION  IN  STARVATION. 


Period. 


15  hours 
6 


3 
6 

3 
II 


D  PER  Hour. 

N  PER  Hour. 

D  :  N. 

2.61 

0-735 
0.720 
0.683 

3-56 

2-39 

0.666 

3.60 

2.51 

0.687 
0.670 

3-65 

2.36 

0.643 

3.66 

2.32 

0.642 

3.62 

^Stiles  and  Lusk:  "American  Journal  of  Physiology,"  1903,  vol.  x,  p.  77. 


STARVATION. 


71 


The  hour-to-hour  sugar  production  from  protein  is  therefore 
even  and  constantly  proportional  to  the  protein  metabolism. 

Parker  and  Lusk^  showed  that  if  benzoic  acid  be  admin- 
istered as  lithium  benzoate  twice  a  day  to  a  fasting  rabbit  the 
animal  will  combine  it  with  the  glycocoll  of  its  metabolism  in 
such  quantity  that  after  a  preliminary  sweeping  out  of  the  gly- 
cocoll contained  in  the  organism  the  amount  eliminated  bears 
a  constant  ratio  to  the  total  nitrogen  elimination  of  the  period. 
In  other  words,  there  is  a  constant  production  of  glycocoll  in  the 
organism  which  is  normally  burned,  but  which  in  this  case  is 
combined  with  benzoic  acid  and  eliminated  in  the  urine.  The 
formula  representing  the  formation  of  hippuric  acid  is  as  follows: 

QH5COOH  +  XH,CHjCOOH  =  CfiHsCO.NHCHjCOOH  +  HjO 
Benzoic  Acid.  Glycocoll.  Hippuric  Acid. 

The  results  of  the  experiment  indicate  a  production  of  3.98 
grams  of  glycocoll  from  the  metabolism  of  100  grams  of  body 
protein.  The  following  table  begins  with  the  fifth  fasting  day 
and  the  second  of  benzoate  feeding,  and  is  as  follows: 


COXST.\NT  RATIO  BETWEEN  GLYCOCOLL  PRODUCTION  AND 
N  ELIMINATION  IN  STARVATION. 


Hippuric  .\cid 


Ratio  Hippuric  Acid 

(or  Glycocoll) 

\  :  Total  X. 


5th  day  of  fast '  0.990  '         0.7060 

6th     "    "      "    1.087  0.6340 

7th     "    "      "    0.775  0.4944 

8th     "    "      "    1. 148  0.5760 

9th     "    "      "    1  0.515  0.3252 


I  :  18.0 

I  :  21.6 

I  :  19.8 

I  =25-5 

I  :  21.8 


The  average  ratio  is  i  :  21.5.  The  glycocoll  production 
seems  therefore  a  normal  and  con.stant  factor  of  the  protein 
metaboli.sm.  Horse's  urine  taken  at  random  showed  ratios  of 
I  :  15  and  1:17  ("see  page  133). 


'  Parker  and  Lusk:  "American  Journal  of  Physiology,"  1900,  vol.  iii,  p.  478. 


72  SCIENCE    OF   NUTRITION. 

The  length  of  life  under  the  condition  of  starvation  generally 
depends  upon  the  quantity  of  fat  present  in  the  organism  at  the 
start.  The  quantity  of  fat  and  protein  in  an  animal  at  the 
beginning  of  starvation  or  at  any  time  during  starvation  may  be 
estimated  if  the  day-to-day  metabolism  be  determined  and  if 
the  whole  animal  be  analyzed  for  fat  and  protein  at  the  time  of 
death.  The  sum  of  the  quantities  remaining  in  the  body,  and 
the  quantity  of  waste  of  previous  days,  will  give  the  composition 
of  the  animal  at  any  definite  date  during  the  experiment.  E. 
Voit^  shows  that  a  rabbit  with  an  original  fat  content  of  7  per 
cent,  lived  nineteen  days  and  lost  49  per  cent,  of  his  body  pro- 
tein. Another  rabbit  with  an  original  fat  content  of  only  2.3  per 
cent,  lived  but  nine  days,  while  the  loss  of  body  protein  amounted 
to  35  per  cent.  At  the  death  of  these  rabbits  the  amount  of  fat 
found  was  very  small,  and  the  general  vitality  toward  the  end 
was  almost  exclusively  maintained  by  the  combustion  of  protein. 
Other  animals,  however,  which  lost  22  to  26  per  cent,  of  their 
protein  contained  considerable  fat  at  the  time  of  death.  E.  Voit 
finds  that  the  greater  the  amount  of  fat  in  the  body,  the  less  is 
the  protein  metabolism.  In  animals  of  equal  fat  content  the 
relation  between  the  amount  of  fat  and  the  amount  of  protein 
oxidized  in  the  cells  in  starvation  is  always  the  same.  When 
there  is  no  fat,  protein  may  burn  exclusively.  From  this  it 
follows  that  the  quantity  of  the  protein  metabolism  in  starvation 
depends  upon  the  amount  of  fat  in  the  body. 

E.  Voit^  has  prepared  the  following  table  from  an  experiment 
of  Schondorff  ^  upon  a  fasting  dog.  The  quotient  ^j^^^t  gives 
the  ratio  between  these  two  components  of  the  organism  at 
the  time  specified.  The  ratio  ^^SlfSiT  gives  the  percentage 
of  the  total  energy  derived  from  the  protein  metabolism.  The 
dog  died  on  the  thirty-eighth  day  of  his  fast. 

^E.  Voit:   "Zeitschrift  fiir  Biologic,"  1901,  Bd.  xli,  p.  545. 

^E.  Voit:   Loc.  cit.,  p.  520. 

^Schondorfif:   "Pfliiger's  Archiv,"  1897,  Bd.  Ixvii,  p.  430. 


STARVATIOX, 


73 


PROTEIN  METABOLISM  IN  STARVATION  AS  INFLUENCED  BY 
THE  FAT  CONTENT  OF  THE  ANIMAL. 


Starvation 
Day. 


Weight 
IN  Kg. 


N  Content 


Fat  Content. 


EXCRZT.\ 

N 
IN  Grams. 


Energy  per 

Sq.  Meter 

Surface. 


Energy  Protein 


Energy  Total. 
Reduced  to  % 


ist  to  3d 

4th  to  13th 

14th  to  15th 

1 6th  to  23d 

24th  to  30th 

31st  to  35th 

36th 

37th 

3Sth 


0.25 
0.29 

0-34 
0.40 

0.57 
0.87 
1. 19 
1-34 
1-51 


7.91 
5-38 
5-70 
5-71 
5-92 
6.62 
7.41 
8.41 
8.89 


1040 
974 
959 
944 
919 
901 


881 


26.5 
16.2 
18.1 
19.1 
21.3 
25.6 

29-5 
33-8 
36.6 


E.  Voit  finds  that  the  amount  of  protein  metabolism  depends 
so  absolutely  upon  the  relation  between  the  amount  of  fat  and 
protein  in  the  body  (the  ^at^t°nt)  ^^^^j  knowing  this  ratio, 
he  says  he  can  estimate  the  relative  protein  metabolism.  When 
the  ratio  rises  to  4.84  in  the  rabbit,  then  98.3  per  cent,  of  the 
total  energy  may  be  derived  from  protein.  Had  fat  still  been 
present  in  considerable  quantity  the  protein  metabolism  would 
have  remained  low.  This  is  the  law  which  governs  the  gradual 
rise  in  the  protein  metabolism  during  starvation,  the  "pre- 
mortal rise,"  it  has  been  termed.  The  increased  combustion 
of  the  protein  is  due  to  the  requirement  for  energy  in  an  organ- 
ism which  has  a  constantly  decreasing  amount  of  fat  upon  which 
to  draw. 

The  actual  loss  of  body  weight  is  greater  when  protein  is  the 
source  of  energy  than  when  the  energy  is  derived  from  fat.  The 
reason  for  this  is  that  if  one  gram  of  nitrogen  is  lost  there  is  a 
diminution  of  body  weight  of  jiZ  grams,  which  represents  just  so 
much  tissue  waste,  and  an  energy  yield  of  0.8  calories  per  gram 
of  "flesh"  lost,  while  the  combustion  of  one  gram  of  fat  simply 
causes  the  loss  of  one  gram  in  body  weight  with  an  energy 
yield  of  9.3  calories.  To  obtain  equivalent  amounts  of  energy 
there  must  therefore  be  a  destruction  of  ele\en  and  a  half  times 
more  "flesh"  by  weight,  than  when  fat  is  oxidized. 


74  SCIENCE    OF   NUTRITION. 

Rubner^  has  maintained  a  dog  for  a  long  period  on  a  diet  of 
fat  which  was  sufficient  in  amount  to  cover  the  energy  require- 
ment. The  content  of  body  nitrogen  fell  from  358.3  grams  to 
166.0  grams,  a  loss  of  53.7  per  cent.  Rubner  finds  that  during 
the  whole  period  the  daily  waste  of  nitrogen  is  0.9  gram  per  100 
grams  contained  in  the  body.  This  "wear  and  tear"  quota  is 
therefore  a  function  of  the  intensity  of  the  life  processes,  being 
proportional  to  the  amount  of  protoplasmic  material  present. 

What  is  the  cause  of  death  from  starvation?  It  does  not 
seem  to  be  due  to  an  essential  change  in  the  composition  of  the 
cells  themselves,  for  no  chemical  alteration  has  been  detected 
in  them.^  What,  then,  is  the  cause  of  death?  The  general 
argument  of  E.  Voit  is  as  follows:  It  must  be  due  either  to  a 
general  failure  of  all  the  cells  or  injury  of  certain  organs  which 
are  necessary  for  life.  If  the  first  cause  were  the  true  cause, 
then  death  would  take  place  when  a  certain  definite  percentage 
of  protein  loss  occurred.  This  does  not  happen,  since  the  body 
loss  at  the  time  of  death  may  vary  between  20  and  50  per  cent, 
of  its  original  protein  content.  When  the  genital  organs  of  the 
salmon  develop  at  the  expense  of  the  liquefying  muscle  substance 
brought  them  by  the  blood,  not  a  single  muscle  cell  of  the  fish  is 
killed,  even  though  these  lose  55  per  cent,  of  their  protein  in 
the  process  (Miescher).  It  seems  extremely  improbable,  then, 
that  a  much  smaller  loss  of  protein  in  starvation  can  be  the 
cause  of  general  cellular  death.  On  the  other  hand,  if  death 
be  due  to  the  failure  of  certain  organs,  especially  important 
to  life,  the  cause  is  to  be  found  in  two  factors:  Either  these 
organs  receive  too  little  nutrition  for  their  proper  functioning, 
or  they  become  so  emaciated  that  they  fail  in  spite  of  sufficient 
nutriment.  Either  the  fuel  is  insufficient  or  the  machine  wears 
out. 

'Rubner:   "Archiv  fiir  Hygiene,"  1908,  Bd.  Ixvi,  p.  49. 
2  Abderhalden,  Bergell,  and  Doerpinghaus:   "Zeitschrift  fiir  physiologische 
Chemie,"  1904,  Bd.  xli,  p.  153. 


STARVATION. 


75 


The  following  table  gives  some  answer  to  this.  The  general 
arrangement  is  in  the  order  of  the  greater  original  fat  content  of 
the  animals : 


IXFLUENXE  OF  FAT  CONTENT  ON  PROTEIN  METABOLISM  AND 
ON  LENGTH  OF  LIFE  IN  STARVATION. 


Animal. 


Dog 

Fowl 

Guinea-pig . . 

Dog 

Fowl 

Rabbit 

Rabbit 

Rabbit 

Fowl 

Rabbit 

Rabbit 


First 

Weight 

Kg. 


20.64 

1-95 
0.67 

23-05 
1. 00 

I-5I 
2-53 
2.34 
1.89 
2.08 
2.99 


Fat  in  %.  Loss  in  %. 


Start.      End.   1  Animal.  Body  N. 


19 

26 

16 

II 
9.1 
7-1 
6.3 
6.3 
2.7 

2.3 

2-3 


1-7 
0.7  I 
0.4  I 
0-5 
o-S 
0.7 
0.4 
0-3 


28 
42 
38 
34 
39 
49 
44 
41 
34 
35 
32 


26 
26 
35 
37 
49 
49 
45 
41 
38 
35 


Days  Be- 
fore Death I 
FROM  Star- 
vation. 


Author. 


30 
35 
10 

38 
12 

19 

19 

19 

9 


Falk. 

Schmanski. 

Rubner. 

Schondorff. 

Kuckein. 

Rubner. 

Koll. 

Rubner. 

Kuckein. 

Kaufman. 

Rubner. 


In  the  first  three  animals  a  large  amount  of  fat  was  present 
at  the  time  of  death,  and  this  had  prevented  a  great  tissue 
waste.  Abundant  food  was  therefore  available  for  the  cells. 
The  cause  of  death  seems,  therefore,  to  be  in  a  reduction  of 
activity  in  one  or  more  organs  important  for  life. 

Again,  if  the  protein  loss  be  kept  down  by  administering  pro- 
tein in  quantity  insufficient  for  the  heating  demands  of  the  organ- 
ism, the  animal  is  kept  living  largely  on  his  own  fat.  Schulz ' 
in  this  way  kept  two  dogs  alive  for  twenty-eight  and  thirty-eight 
days,  with  losses  of  body  nitrogen  amounting  to  only  i8  and  7 
per  cent,  of  the  original  quantity.  The  fat  present  was  only 
0.4  to  0.5  per  cent,  at  the  end.  These  dogs  certainly  suffered 
from  no  general  loss  of  cell  tissue.  E.  Voit  concludes  that  death 
jrom  starvation  is  primarily  due  to  loss  oj  substance  in  organs  im- 
portant to  lije,  but  it  may  also  ensue  under  certain  circumstances 
as  a  result  oj  deficient  nutrition  to  these  organs. 


'Schulz:   "Pfluger's  Archiv,"  1899,  Bd.  Ix.xvi,  p.  379. 


^6  SCIENCE    OF   NUTRITION. 

Schulz^  and  his  pupils  let  a  dog  which  was  fat  and  well 
nourished  fast  for  twenty-seven  days.  On  the  twenty-fifth  day 
the  animal  manifested  weakness,  which,  on  the  twenty- seventh 
day,  appeared  to  threaten  its  life.  Then  for  a  day  400  c.c.  of 
milk  were  given  to  the  dog  and  on  four  subsequent  days  300 
grams  of  meat  each  day.  Although  these  quantities  of  food 
were  greatly  under  the  quantity  required  to  maintain  the  dog 
without  loss  of  body  fat,  still  the  animal  recovered  its  strength, 
added  7.3  grams  of  protein  nitrogen  to  its  body,  and  then  lived 
during  a  second  period  of  sixty-one  days  of  starvation.  During 
this  second  fasting  period  the  protein  metabolism  was  on  a 
much  lower  level  than  during  the  first  period.  Schulz  notices 
that  when  the  fasting  dog  still  contains  considerable  fat,  protein 
in  the  food  is  readily  retained,  even  though  the  content  of  energy 
ingested  be  under  the  body's  needs.  When,  however,  the  body 
fat  is  nearly  exhausted,  all  the  ingested  protein  and  some  body 
protein  besides  is  destroyed  to  provide  for  the  support  of  the 
organism.  Schulz  concludes  that  death  from  starvation  is  due 
to  auto-intoxication,  a  condition  which  was  relieved  in  the  fasting 
experiment  mentioned  above  by  the  ingestion  of  meat. 

The  question  of  what  organs  are  attacked  in  starvation  has 
attracted  attention.  Long  ago  Voit^  showed  that  the  muscles 
of  a  cat  which  starved  thirteen  days  lost  30  per  cent.,  while  heart, 
brain,  and  cord  lost  3  per  cent.  only.  In  normally  nourished 
animals  E.  Voit  finds  that  the  relative  weights  of  the  fat-free 
organs  in  animals  of  the  same  species  are  very  constant.  He^ 
uses  Kumagawa's*  results  to  show  what  percentage  the  different 
organs  represent  in  the  fat-free  organism  of  a  dog  before 
and  after  a  twenty-four- day  fast.  The  third  column  repre- 
sents the  percentage  loss  of  the  fat-free  organ  in  starvation: 

^Schulz:   "Pfliiger's  Archiv,"  1906,  Bd.  cxiv,  pp.  419  to  462. 

^Voit:  "Zeitschrift  fiir  Biologic,"  1866,  Bd.  ii,  p.  353. 

^E.  Voit:  Ibid.,  1904,  Bd.  xlvi,  p.  195. 

^Kumagawa:  "  Aus  den  Mittheil.  d.  med.  Fakultat  der  kais.  Japan.  Univ.," 
Tokio,  Bd.  iii.  No.  i. 


STARVATION.  ^y 

LOSS  IN  WEIGHT  OF  DIFFERENT  ORGANS  DURING  STARVATION. 


Organ. 


Skeleton 

Skin 

Muscles 

Brain  and  Cord 

Eyes 

Heart 

Blood 

Spleen 

Liver 

Pancreas 

Kidney 

Genitals 

Stomach  and  intestine 
Lungs 


Fat-free  Animal  Contains  in 
Percentage  of  Weight. 


Well  Nourished,  i       Starvation. 


14 


53 


.78 
3° 
77 
0.94 
o.ii 

0-54 
7.14 

0-39 
3-98 

0-33 
0.66 
0.30 
5-8i 


21.50 
11.29 

48.39 
I. II 
0.16 
0.69 

5-69 
0.26 

3-05 
0.19 

0-4S 
0.23 
6.02 
0.97 


Fresh  Fat-free 
Organ  Loses  in 

Percentage 

Weight  during  a 

24  Days'  Fast. 


5 
28 
42 
22 

3 
16 


57 
50 
62 

55 
49 
32 
29 


It  is  apparent  that  the  greatest  loss  is  from  the  glands  and  the 
least  from  the  skeleton.  The  activity  of  the  glands  is  greatly 
reduced  in  starvation.  Luciani  found  that  there  was  no  gastric 
juice  formed  during  Succi's  thirty-day  fast,  but  Langley  and 
Edkins  find  pepsinogen  stored  within  the  cells  of  the  gastric 
glands.  The  bile  flow  continues  up  to  the  death  of  the  person, 
but  in  diminished  quantity,  corresponding  to  the  lack  of  food 
and  the  decreasing  size  of  the  liver.  The  writer^  has  noticed 
a  great  reduction  in  the  activity  of  the  milk  secretion  in  starving 
goats,  there  being  a  permanent  cessation  of  flow  after  five  days. 
The  percentage  of  fat  increases  in  the  milk,  as  it  does  in  the 
blood,  liver,  and  other  organs.'  The  fasting  organs  attract  fat 
from  the  fat  deposits  of  the  body  and  it  is  brought  to  them  by 
the  circulating  blood.  Dextrose  is  present  in  the  blood  up  to 
the  last  day  of  life,  having  its  probable  origin  in  a  constant 
production  of  sugar  in  protein  metabolism.  The  composition 
of  the  plasma  of  the  blood  in  fasting  as  regards  its  protein  con- 
stituents  varies   very    slightly    from    the    normal.     Lewinski^ 

'Lusk:   Voit's  Festschrift,  "Zeitschrifl  fur  Biologic,"  1901,  Bd.  xlii,  p.  41. 
'Rosenfeld:   "Ergebnissc  der  Physiologic,"  1903,  Bd.  ii,  i,  p.  50. 
'Lewinski:   "Pfliiger's  Archiv,"  1903,  Bd.  c,  p.  631. 


78 


SCIENCE    OF   NUTRITION. 


gives  the  following   comparative  analyses  of  blood-plasma  of 
dogs: 

loo  C.C.  BLOOD-PLASMA  CONTAIN  OF  GRAMS  N: 


/  Fasting 
\  Fed--.. 
/  Fasting 
\  Fed... 

^       ^^^        f  Fasting, 

Dog  III..   J    Fed.... 

[  Fasting 

/  Fasting 

\  Fed.... 


Dog  I... 
Dog  II.. 


Dog  IV.. 


Total. 

Albumin. 

Globulin. 

0.257 
0.240 

0-93S 
0.831 

0.621 
0.511 

0.921 
1.062 

0-313 

0-515 

0.544 
0,423 

1. 010 
0.977 
1.096 

0.467 
0.475 
0-554 

0.450 
0.402 
0.443 

1.052 
0.877 

0-536 
0.542 

0.324 
0.248 

Fibrin- 
ogen. 


0.057 
0.080 
0.064 
0.124 
0.093 

O.IOO 

0.099 
0.192 
0.087 


The  only  constant  change  seems  to  be  a  slight  increase  of 
globulin  during  fasting.  Burckhardt  believes  this  to  be  due  to 
the  passage  of  globulins  from  the  tissues  to  the  blood.  The 
percentage  of  hemoglobin  and  the  number  of  blood-corpuscles 
are  not  appreciably  affected.  It  is  evident  then  that  the  blood  in 
starvation  retains  the  normal  composition  as  regards  its  nutrient 
materials,  except  that  it  carries  fat  in  increased  quantity  to 
the  cells.  In  general  the  cells  are  well  nourished  for  the  ordi- 
nary maintenance  of  the  life  functions.  Hence  the  appetite 
is  not  an  expression  of  general  cellular  hunger,  but  rather  the 
result  of  a  local  condition  of  the  gastro-intestinal  canal,  which 
stimulates  the  individual  to  replenishment. 

The  glycogen  of  an  animal  is  greatly  reduced  during  star- 
vation, but  after  seventy- three  days  it  is  not  entirely  removed.^ 
Prausnitz^  reports  that  a  dog  weighing  22  kilograms,  after 
fasting  for  twelve  days  and  after  excreting  287  grams  of  sugar  in 
the  urine  as  the  result  of  phlorhizin  injections,  still  contained 
25  grams  of  glycogen  in  his  body.  The  writer^  has  found  0.4 
gram  of   glycogen  in   the  liver   of   a   meat-fed   phlorhizinized 

^  Pfliiger:  "  Pfliiger's  Archiv,"  1907,  Bd.  119,  p.  119. 

^Prausnitz:   "Zeitschrift  fiir  Biologie,"  1892,  Bd.  xxix,  p.  168. 

^  Reilly,  Nolan  and  Lusk:  "American  Jour,  of  Physiol.,"  1898,  vol.  i,  p.  397. 


STARVATION. 


79 


dog  after  eleven  days  of  diabetes  and  an  excretion  of  over  600 
grams  of  sugar.  Exercise  will  greatly  reduce  the  glycogen  con- 
tent, but  the  only  method  of  completely  freeing  the  organism 
of  glycogen  is  by  tetanus.^  Zuntz^  rid  a  rabbit  of  glycogen  by 
strychnin  convulsions  and  then  kept  the  rabbit  fasting  and  under 
the  influence  of  chloral  for  119  hours.  During  this  time  5.25 
grams  of  sugar  were  excreted  in  the  urine  and  yet  1.286  grams  of 
glycogen  were  found  in  the  liver  and  muscles.  This  must  have 
gradually  arisen  from  the  protein  metabolism.  The  writer^ 
made  an  observation  that  in  a  fasting  diabetic  rabbit  tetanus 
produced  an  extra  elimination  of  sugar  in  the  urine  of  i.i  grams, 
which  undoubtedly  was  derived  from  the  glycogen  content  of 
the  organism.  (See  p.  281.)  The  quantity  eliminated  corre- 
sponded to  the  amount  found  as  glycogen  by  Zuntz  as  above 
mentioned. 

There  now  remains  a  discussion  of  the  influence  of  work  and 
of  change  in  temperature  upon  the  fasting  organism. 

FrentzeP  has  shown  the  effect  of  external  work  upon  the 
protein  metabolism  of  fasting  dogs.  One  of  the  dogs  did  an 
amount  of  work  corresponding  to  216,937  kilogrammeters  in 
three  days.  The  protein  metabolism  rose  during  the  working 
hours  and  continued  high  on  the  last  day,  which  was  one  of 
complete  rest.  Frentzel  computes  that  the  nitrogen  elimination 
of  the  last  four  days  (=  20.7  grams)  represents  an  energy 
equivalent  of  220,300  kilogrammeters.  This  could  not  cover 
the  work  done  by  the  dog  if  we  add  to  the  measured  work  that 
which  was  done  by  the  heart  and  respiratory  muscles.  The 
protein  metabolism  of  four  days  is  therefore  entirely  insufficient 
to  cover  the  work  done  during  three.  The  source  of  the  energy 
for  the  work  accomplished  must  be  found  in  an  increased  meta- 
bolism of  fat.     The  increase  in  protein  metabolism  above  that 

'  Kiilz:   Lud wig's  Festschrift,  i8gi,  p.  119. 

*  Zuntz:  Vcrhandl.  der  phvsiol.  Ges.  zu  Berlin,  "Arch,  fiir  Phvsiol.,"  1893, 
p.  378. 

'  Lusl<:  "Zeitschrift  fvir  Biologic,"  1898,  Bd.  xxxvi,  p.  iii. 
*Frentzel:    "Pfluger's  Archiv,"  1897,  Bd.  Ixviii,  p.  212. 


8o 


SCIENCE    OF   NUTRITION. 


of  rest  was  not  sufficient  to  supply  7  per  cent,  of  the  energy 
needed  to  do  the  work.  The  record  of  the  dog's  nitrogen 
metabolism  is  as  follows: 


INFLUENCE  OF  WORK  ON  THE  N    METABOLISM  OF  FASTING 

DOGS. 


Day. 


ist  to  4th 
5th 

6th 

7th 

8th 

9th 

loth 

nth 

12th 


Work  or  Rest. 


Rest. 
Rest. 
Rest. 
Rest. 
Rest. 

Work. 

Work. 

Work. 
Rest. 


Food. 


100  g.  lard. 
100  g.     " 
100  g.     " 
Fasting. 


Grams  of  N  Excreted. 


Per  Day. 


3-^3 
3-52 
3-71 
3-99 

4-97 

5.02 

5-63 
5.08 


Per  Hour. 


0.1304 

0.1467 

0.1546 

0.1663 

*o.368o 

to.  183  7 

*o.275o 

to.  1 960 

*0.2400 

to.233S 
0.2117 


*  Work. 


t  Rest. 


Succi  did  not  show  a  similar  rise  of  protein  metabolism 
from  the  effect  of  work.  The  eleventh  day  of  his  fast  he  spent 
in  bed.  On  the  twelfth  day  he  rode  a  horse  for  an  hour  and 
forty  minutes,  raced  for  eight  minutes  with  some  students,  and 
gave  an  exhibition  of  fencing  in  the  evening.  During  the  day 
he  walked  19,900  steps.  The  urinary  nitrogen  on  the  eleventh 
day  (rest)  was  7.88  g. ;  on  the  twelfth  (work),  7.162;  and  on 
the  days  following  3.50,  5.33,  5.14,  5.05.  The  work  done  was 
evidently  at  the  expense  of  increased  metabolism  of  fat.  That 
this  is  the  case  had  already  been  demonstrated  by  Pettenkofer 
and  Voit.^  A  fasting  man  at  work  showed  no  increase  in  his 
protein  metabolism,  but  the  quantity  of  fat  burned  rose  enor- 
mously. This  is  shown  by  the  following  comparison  of  the 
number  of  grams  of  fat  burned : 


1  Pettenkofer  and  Voit:    "Zeitschrift  fiir  Biologie,"   1866,  Bd. 
C.  Voit:   Ibid.,  Bd.  xiv,  1878,  p.  144. 


ii,  P-  459; 


STARVATION.  ,  8l 

Day.  Night. 

8  A.M.  to  8  P.M.  8  P.M.  to  8  A.M. 

Rest  during  day ii6  g.  94  g- 

Work  during  9  hours  of  day  period 312  g.  7°  g- 

The  fat  metabolism  during  the  day  of  work  is  two-and-a- 
half  times  that  of  the  resting  day  and  is  presumably  the  source 
of  the  energy  for  the  mechanical  work  accomplished.  During 
the  night  following  the  working  day  the  reduction  of  fat  combus- 
tion as  compared  with  the  night  before  is  due  to  more  profound 
sleep. 

Another  phase  of  the  effect  of  work  is  shown  in  the  variation 
between  the  day  and  night  metabolism  of  Tigerstedt's  fasting 
medical  student,  J.  A.  The  average  carbon  dioxid  excretion  in 
grams  for  two-hour  periods  during  five  days  of  fasting  was  as 
follows.  The  figures  showing  the  elimination  during  the  hours 
of  sleep  are  printed  in  black  letters. 

A.  M.  p.  M. 

Time 10-12         12-2       2-4       4-6       6-8     8-10     10-12 

Carbon  dioxid  (grams)  54.8  57.2       54.1      57.8     59.5     66.4     46.5 

A.  M. 

Time 12-2      2-4      4-6      6-8       

Carbon  dioxid  (grams) 37-5     39-i     40.7     68.6       

The  nitrogen  of  the  urine  was  also  less  during  sleep  than 
during  the  waking  hours: 


Fasting  Day. 


N  IN  THE  Urine. 


Day. 


Night  (10  p.  M. 
to  10  a.  m.). 


ISt. 

2d. 

3<i- 
4th 

5th 


7.11 
6.87 
6.83 
7.91 
6.36 


4-93 
5-85 
6.65 

5-65 
4.98 


Johansson'  finds  that  the  inequality  of  night  and  day  metab- 
olism depends  on  muscular  work.     Sitting  up  raises  the  metab- 

'Johansson:   "Skandinav.  Archiv  fiir  Physiologic,"  1898,  Bd.  viii,  p.  109. 
6 


82 


SCIENCE   OF   NUTRITION. 


olism,  and  standing  does  so  still  more.  Even  when  one  lies  in 
bed,  restlessness  during  the  day  may  increase  the  metabolism. 
And  when  perfect  muscular  relaxation  ensues  there  may  still 
be  influences,  such  as  light  on  the  retina  or  sounds,  which  may 
act  reflexly  on  the  organism  and  slightly  increase  the  metabol- 
ism. Johansson  illustrates  these  variations  in  the  following 
comparisons  between  night  and  day  excretion  of  carbon  dioxid 
of  starving  men,  the  night  CO  2  being  figured  at  100. 


Night  CO2. 

Day  CO2. 

100 

105 

100 

no 

100 

142 

100 

128 

100 

147 

Author. 


Complete  muscular  rest 

Ordinary  rest  in  bed 

Ordinary  life  (no  hard  work) 


Johansson. 
Johansson. 
Tigerstedt. 
Pettenkofer  and  Voit. 
Tigerstedt. 


Johansson  agrees  with  Tigerstedt  that  the  minimum  metab- 
olism of  a  man  in  bed  is  represented  by  24  to  25  calories  per 
kilogram  daily. 

The  temperature  of  the  fasting  organism  is  usually  normal. 
Luciani  found  a  normal  temperature  in  Succi  during  his  thirty- 
day  fast.  The  temperature  falls  only  a  few  days  before  death. 
Sonden  and  Tigerstedt^  find  that  the  diurnal  variations  per- 
sist during  fasting  in  their  ordinary  rhythm.  The  average 
temperature  of  the  medical  student  J.  A.  during  his  five-day 
fast  was  but  0.16°  below  his  normal  temperature  when  food  was 
allowed  him.  These  diurnal  variations  are  exactly  concomitant 
with  the  fluctuations  of  carbon  dioxid  excretion  noted  on  a 
previous  page.  When  the  carbon  dioxid  production  increases, 
the  temperature  rises. 

This  parallelism  may  be  easily  shown  by  comparing  the  two 
factors  in  the  chart  (Fig.  2)  as  given  by  Sonden  and  Tiger- 
stedt.^   Furthermore,  the  diurnal  variations  tend  to  disappear  if 

^Sonden  and  Tigerstedt:  "Skandin.  Archiv.  fiir  Physiologie,"  1895, 
Bd.  vi,  p.  136. 

*  Sonden  and  Tigerstedt:    Loc  cit.,  p.  r32. 


STARVATION. 


83 


the  person  be  kept  in  a  state  of  muscular  rest,  so  that  the  output 
of  energy  during  the  day  and  the  night  remains  the  same.     In 

Crams  COz 

her  hoar 

3S 


30 


i5 


10 


15 


10 


... 

— 



h- 

— ^ 

' 

— 

6 

i 

1 

1 

^ 

1 

^,, 

*  ^ 

•f 

i 

i 

1 

0 

/ 

2 

;: 

\ 

f- 

e 

37' 

TeTnfi, 

36* 


I    m$f-t 


Sleep 


^oon. 


Fig.  I. — Curve  of  carbon  dioxid  elimination  compared  with  Jiirgensen's 
curve  of  normal  diurnal  temperature  variation.  This  individual  led  a  normal 
life  and  partook  of  his  usual  nourishment. 

this  state  the  temperature  may  fall  0.6°  below  the  normal  on 
account  of  the  absence  of  muscle  movement.    This  regularity 


84. 


SCIENCE   OF   NUTRITION. 


of  temperature  and  metabolism  is  beautifully  shown  in  the  fol- 
lowing chart  of  Johansson:^ 


GramsCOi 

her  hour 


zsc 


zo^. 


iz      z 
Night 


Ifoon. 


37° 

Teml> 

56° 


Jii^fit 


Fig.  2. — Carbon  dioxid  elimination  and  body  temperature  in  fasting  and  com- 
plete muscular  rest. 


Inversion  of  the  normal  routine  of  life,  so  that  one  sleeps  in 
the  daytime  and  is  awake  and  active  at  night,  brings  about  an. 
inversion  of  the  curve  of  body  temperature.  This  is  well  shown 
in  the  monkey.^ 

Gibson^  travelled  half  way  round  the  world  in  making  a  trip 

*  Johansson:   Loc.  cit.,  p.  142. 

^  Goldbraith  and  Simpson :  Proceedings  of  the  Physiological  Society,  "  Jour- 
nal of  Physiology,"  1903,  vol.  xxx,  p.  xx. 

^Gibson:  "American  Journal  of  the  Medical  Sciences,"  June,  1905. 


STARVATION.  85 

from  New  Haven,  Connecticut,  to  Manila,  and  then  returned. 
He  found  that  the  rhythm  of  daily  variation  was  dependent  on 
the  time  of  the  solar  day  and  was  independent  of  the  part  of 
the  world  in  which  he  happened  to  be. 

Benedict,^  however,  was  unable  to  obtain  any  inversion  of 
the  curve  of  normal  body  temperature  in  men  who  worked  dur- 
ing the  night  and  slept  during  the  day. 

'Benedict:   "American  Journal  of  Physiolog}',"  1904,  xi,  p.  145. 


CHAPTER  III. 


THE  REGULATION  OF  TEMPERATURE. 

It  has  been  seen  that  the  temperature  of  a  warm-blooded 
animal  is  maintained  at  the  normal  throughout  a  fast.  Not 
only  this,  but  it  is  maintained  at  the  same  level,  even  though  the 
temperature  of  the  outside  environment  vary  from  o°  and  lower 
to  30°  to  35°.  In  cold-blooded  animals  the  temperature  of  the 
body  is  only  slightly  higher  than  that  of  their  environment  at 
the  time.  The  metabolism  of  such  animals  varies  with  the 
temperature.  The  frog  in  the  mud  during  the  winter  at  a 
temperature  of  4°  C.  has  quite  a  different  metabolism  from  that 
which  he  enjoys  during  the  summer  sunshine  as  he  sits  on  the 
river-bank  or  snaps  at  passing  flies.  The  curve  of  his  carbon 
dioxid  elimination  at  various  temperatures  has  been  made  by 
E.  Voit  from  the  analyses  of  H.  Schultze,  and  is  given  below : 

COzinmff. 
f>er/!g.cf 


SOO 


4C0. 
300 


200 
100 

o 


"7^*  JcT'^  30-         Temjo. 

Fig.  3. — CO2  in  milligrams  per  hour  per  kg.  frog. 

A  sudden  rise  in  the  frog's  metabolism  commences  at  about  20°. 
A  temperature  of  20°  corresponds  to  that  of  the  bear  and  marmot 
during  their  winter's  hibernation,  and  is  a  level  of  compara- 

86 


THE  REGULATION  OF  TEMPERATURE.  87 

tively  low  metabolism.  This  reduction  in  activity  is  exem- 
plified by  the  fact  that  a  cat  whose  temperature  has  been  artifi- 
cially reduced  to  19°  may  have  but  one  heart-beat  per  minute.^ 
At  the  time  of  hibernation  the  marmot  lives  at  the  expense  of 
fat  and  retains  some  glycogen  within  its  muscle  tissue.  The 
metabolism  may  correspond  to  only  one-twentieth  the  amount 
of  energy  used  during  the  period  of  activity.  During  the  process 
of  waking  from  the  winter  sleep  the  glycogen  stored  in  the 
muscles  is  drawn  upon.^ 

E.  Voit^  has  drawn  attention  to  the  fact  that  the  above  curve 
of  increasing  metabolism  with  increasing  temperature  corre- 
sponds to  the  increasing  ability  of  the  frog's  muscle  to  contract, 
and  to  the  increasing  effectiveness  of  enzymotic  activity.  A 
high  temperature  is  necessary  for  the  irritability  and  activity  of 
protoplasm.  The  warmth  of  the  sunshine  increases  the  irri- 
tability of  the  protoplasm  of  the  tree  in  the  spring,  with  the 
resulting  development  of  the  foliage.  Warmth,  however,  is  not 
the  cause  0}  the  metabolism,  but  only  one  0}  the  conditions  for  it. 
In  warm-blooded  animals  the  temperature  is  maintained  at  a 
constant  level  independent  of  climatic  conditions,  and  this  level 
is  a  favorable  one  for  the  activity  of  nerve  and  muscle.  It  would 
indeed  be  inconvenient  were  the  active  life  of  a  man  dependent 
upon  the  temperature  of  his  environment.  The  essential 
mechanism  for  the  regulation  of  the  body  temperature  is  through 
the  nerves.  The  action  of  cold  on  the  skin  may  stimulate  its 
peripheral  nerve-endings,  which  are  sensitive  to  cold,  and  re- 
flexly  efifect  in  the  organism  a  greater  heat  production,  and  a 
vaso-constriction  of  peripheral  blood-vessels;  the  action  of  heat, 
on  the  contrar}',  effects  vasodilatation  and  production  of  sweat. 
It  is  believed  that  the  cold-blooded  progenitors  of  warm-blooded 
animals  changed  their  habitat  from  the  sea  to  the  land  at  a 
tropical  temperature  which  is  at  present  possessed  by  their 

'  Simpson  and  Herring:  "Journal  of  Physiology,"  1905,  vol.  xxxii,  p.  305. 

^  Weinland  and  Riehl:  "Zeitschrift  fur  Biologic,"  1908,  Bd.  1,  p.  75. 

'  E.  Voit:  "Sitzungsber.  der  Ges.  fiir  Morph.  und  Physiol.,"  1896,  licft  III. 


88  SCIENCE    OF   NUTRITION. 

descendants.  In  the  course  of  development  these  animals 
acquired  the  power  to  maintain  that  ancestral  temperature, 
which  proved  favorable  for  the  activity  of  their  body  substance. 
The  nervous  mechanism  through  which  this  is  accomplished  is 
twofold:  First,  there  is  an  increased  production  of  heat  in  the 
presence  of  external  cold  {the  chemical  regulation  of  temperature), 
and,  second,  variations  in  the  quantity  of  blood  supplied  to  the 
skin  modify  loss  of  heat  by  radiation  and  conduction  and 
variations  in  the  amount  of  sweat  modify  the  loss  of  heat  by 
evaporation  of  water  (these  are  the  factors  of  the  physical  regula- 
tion of  temperature).  The  great  importance  of  these  two  con- 
trolling influences  will  be  seen  as  the  subject  develops. 

If  the  body  were  a  mass  of  cells  having  the  shape  of  a  ball 
with  a  constant  heat  production  in  its  center,  it  would  be  easy 
to  calculate  its  temperature  in  the  different  zones  of  the  interior. 
The  loss  of  heat  from  the  surface  would  obviously  be  equal  to 
the  heat  production,  if  the  temperature  of  the  various  zones 
continued  constant. 

If  two  balls  of  the  same  material,  but  of  unequal  size,  were 
equally  warm,  the  smaller  would  cool  more  quickly  than  the 
larger  on  account  of  the  relatively  greater  exposed  surface  from 
which  heat  could  be  discharged.  The  heat  elimination  would 
be  proportional  to  the  surface  exposed. 

To  determine  the  surface  of  geometrically  similar  solids, 
and  hence  of  animals  of  similar  shapes,  the  following  formula 
was  used  by  Meeh,^  in  which  S  =  surface  and  V  =  volume : 

v§-    V 

Since  animals  contain  the  same  materials,  one  may  substitute 
W  =  weight  for  V. 

Then  the  value  of  L.  may  be  empirically  determined  for 
each  shape  or  animal,  and  this  value  =  k.  Hence  the  formula 
would  read: 

^  =  korS  =  kfW^ 
^Meeh:   " Zeitschrif t  fiir  Biologie,"  1879,  Bd.  xv,  p.  425. 


THE  REGULATION  OF  TEMPERATURE.  89 

The  value  of  k  or  the  constant  in  the  relationship  of  weight 
to  surface  in  each  animal  has  been  given  by  Rubner  as  follows : 

Man 12.3 

Dog. 1 1. 2-10. 3 

Rabbit 12. 9-12.0 

Rabbit  (without  ears) 10.8 

Calf 10.5 

Sheep 12. 1 

Cat 9.9 

Pig -. 8.7 

Guinea-pig 8.5 

Fowl 10.4 

Rat 9.1 

White  mouse 1 1 .4 

To  compute  the  body  surface  of  a  man,  for  example,  the 
formula  12.3^  (body- weight)  ^  would  be  employed. 

The  use  of  the  above  formula  rendered  possible  the  calcu- 
lation of  the  heat  elimination  per  unit  of  area  in  fasting  animals 
during  rest.  When  these  have  been  previously  well  fed,  there 
is  a  surprising  uniformity  of  result.  It  is  Rubner's  law  that  the 
metabolism  is  proportional  to  the  superficial  area  of  an  animal. 
In  other  words,  the  metabolism  varies  as  the  amount  of  heat 
loss  at  the  surface,  and  its  variation  in  accordance  with  this  law 
is  necessary  for  the  maintenance  of  a  constant  temperature. 

Erwin  Voit^  has  calculated  the  following  general  table 
showing  the  heat  production  in  resting  animals  of  various  sizes 
at  medium  temperatures  of  the  environment: 

Calories  Produced. 

Weight  in  Kg.  Per  Kilo.  Per  Sq.  M.  Surface. 

Horse 441                          11.3  948 

Pig 128                           19. 1  1078 

Man 64.3                       32.1  1042 

Dog 15.2                       51.5  1039 

Rabbit 2.3                      75.1  776 

Goose 3.5                      66.7  969 

Fowl 2.0                      71.0  943 

Mouse^ 0.018  212.0  1188 

Rabbit '  (without  ears)....     2.3                        75.1  917 

The  universality  of  this  law  of  Rubner's  is  remarkable.  Even 
at  a  room  temperature  of  30°  where  all  thermal  influence  is 
removed,  two  guinea-pigs  of  different  sizes  will  produce  heat  in 

'E.  Voit:    "Zeitschrift  fur  Biologic,"  1901,  Bd.  xli,  p.  120. 
*  Rubner:   "Energiegesetze,"  1902,  p.  282. 


90 


SCIENCE    OF   NUTRITION. 


proportion  to  their  surface.  In  this  case  there  is  a  minimum  of 
heat  production  determined  for  the  resting  organism  according 
to  the  law  of  superficial  area. 

When  this  discovery  was  first  made,  the  interpretation  was 
offered  that  the  variation  in  the  metabolism  of  different  animals 
in  proportion  to  the  skin  area  was  due  to  the  "chemical  regula- 
tion" brought  about  by  the  specific  sensory  influences  of  cold 
proceeding  from  a  definite  area  of  surface.  This  explanation 
fell  when  Rubner  discovered  that  at  a  temperature  of  30°,  under 
which  condition  all  thermal  stimulus  to  the  organism  ceased, 
two  guinea-pigs  of  different  sizes  still  produced  heat  in  proportion 
to  their  skin  areas.  A  similar  fact  was  noted  by  Frank  and  Voit,^ 
who  found  that  the  administration  of  curare,  which  paralyzes 
the  voluntary  muscles,  scarcely  affected  the  carbon  dioxid  output 
of  a  dog  as  compared  with  what  was  eliminated  during  ordinary 
muscular  rest,  provided  the  temperature  of  the  animal  was 
maintained  at  the  normal  by  keeping  him  in  a  warmed  chamber. 
The  mass  of  living  cells  preserved  the  same  metabolism  as  before, 
even  though  a  pathway  of  heat  increase  had  been  cut  off  through 
paralysis  by  curare  of  the  motor  nerve-endings  in  the  muscles. 
Keeping  the  animal  in  a  warmed  chamber  was  necessary  in  this 
case,  for  Rohrig  and  Zuntz^  had  shown  that  curarized  animals 
at  the  ordinary  room  temperature  lost  the  power  of  maintaining 
their  body  temperature  and  that  their  metabolism  decreased 
accordingly.  The  removal  of  the  chemical  regulation  caused 
a  behavior  toward  external  temperature  similar  to  that  of  cold- 
blooded animals. 

Although  the  effect  of  cold  on  the  skin  (inducing  chemical 
regulation)  is  of  itself  demonstrably  insufficient  to  account  for 
the  "law  of  skin  area,"  Rubner^  argues  that  even  at  30°  C, 
when  the  body  is  losing  heat  by  means  of  the  dilatation  of  the 
blood-vessels  and  the  evaporation  of  water  (physical  regulation), 

'Frank  and  Voit:   "Zeitschrift  fiir  Biologie,"  1901,  Bd.  xlii,  p.  309. 
^Rohrig  and  Zuntz:   "Pfliiger's  Archiv,"  1S71,  Bd.  iv,  p.  57. 
^Rubner:   " Energiegesetze,"  1902,  p.  174. 


THE    REGULATION   OF   TEMPERATURE.  9I 

the  law  is  still  a  necessity  if  the  general  mechanism  for  loss  of 
heat  in  the  various  animals  is  the  same  in  all.  An  infant  pro- 
duces 90  calories  per  kilogram  in  twenty-four  hours,  an  adult 
32  calories.  Were  the  metabolism  of  an  adult  90  calories  per 
kilogram,  the  means  of  heat  elimination  through  his  compara- 
tively smaller  surface  would  have  to  be  materially  modified 
if  a  normal  temperature  were  to  be  maintained  with  comfort. 

The  organism  therefore  preserves  the  tropical  temperature 
of  its  cells  at  the  expense  of  a  metabolism  which  is  proportional 
to  the  skin  area  of  the  individual. 

The  loss  of  heat  by  an  organism  is  by  the  following  paths: 

1.  Conduction  and  radiation. 

2.  Evaporation  of  water  from  lungs  and  skin. 

3.  Warming  the  food  ingested. 

4.  Warming  the  inspired  air  (conduction). 

The  great  outlets  for  heat  loss  are  by  conduction  and  radia- 
tion (of  which  in  the  dog  97.3  per  cent,  takes  place  through  the 
skin  and  2.7  per  cent,  through  the  lungs ^)  and  through  the 
evaporation  of  water.  The  losses  through  warming  the  food, 
and  through  heat  of  the  urine  and  of  solution  of  urinary  con- 
stituents, through  the  feces  and  the  warming  of  expired  carbon 
dioxid  may  be  ordinarily  disregarded. 

The  pathway  for  the  loss  of  heat  varies  with  the  temperature 
of  the  environment.  At  a  low  temperature  there  is  little  evapo- 
ration of  water,  and  at  a  temperature  of  37°  there  can  be  no  heat 
loss  by  radiation  and  conduction  (except  by  a  rise  in  body 
temperature)  and  water  evaporation  removes  the  whole  of  it. 
In  the  dog  at  a  high  temperature  there  is  spreading  out  of  the 
limbs  to  promote  heat  loss  by  radiation  and  conduction,  and 
rapid  breathing  (polypnea)  with  extension  of  the  hyperemic 
tongue  to  promote  evaporation  of  water.  In  the  horse  and  in 
man  there  is  especially  an  outbreak  of  sweat,  which  is  not  pos- 
sible in  the  dog  as  its  skin  does  not  secrete  sweat. 

It  has  been  seen  that  Lavoisier  noticed  that  cold  increases 
the  metabolism.     This  has  been  abundantly  confirmed.     The 

•Rubner:   "Energiegesetze,"  1902,  p.  187. 


92 


SCIENCE    OF    NUTRITION, 


simplest  illustration  of  this  action  is  to  be  found  in  fasting 
animals.  Rubner  has  called  this  increase  of  metabolism,  and 
therefore  of  heat  production,  the  chemical  regulation  of  the  body 
temperature.  It  is  the  same  as  burning  more  coal  in  the  fur- 
nace on  a  cold  day  in  order  to  maintain  the  temperature  of  the 
house.  Volt  had  previously  demonstrated  this  action  in  the 
case  of  a  man  (see  below). 

It  will  become  apparent  as  the  discussion  proceeds  that  a 
constant  basic  quantity  of  energy  is  necessary  to  maintain  the 
life-processes  of  a  warm-blooded  animal  situated  in  a  tropical 
environment.  In  this  case  the  energy  of  metabolism  is  directly 
concerned  in  maintaining  the  vibrant  motions  of  the  protoplasm 
(see  p.  360)  and  heat  production  is  a  secondary  result.  If  now 
the  organism  be  subjected  to  the  influence  of  a  cold  environment 
there  is  an  increased  production  of  heat  which  is  directly  derived 
from  metabolized  substances  and  the  mission  of  which  is  to 
maintain  the  temperature  of  the  body  at  the  tropical  point. 
It  will  also  be  shown  in  another  place  how  this  passive  increase 
in  heat  production  through  "chemical  regulation,"  may  become 
imnecessary  if  instead  the  needed  heat  be  obtained  from  other 
sources,  as  from  the  increased  heat  production  incident  to 
muscular  work  or  to  food  ingestion. 

Rubner  placed  a  fasting  guinea-pig  in  a  bell- jar  which  was 
ventilated  so  that  the  carbon  dioxid  production  could  be  deter- 
mined. The  temperature  of  the  bell- jar  could  be  changed  by 
immersing  it  in  water.     The  following  were  the  results : 

ACTION    OF    CHEMICAL    REGULATION    IN    THE    GUINEA-PIG. 


Temp,  op  Air. 


0.0" 
11.1° 
20.8° 
25-7° 
?,<^-?,° 
34-9° 
40.0° 


Temp,  of  Animal. 


Grams  of  CO2  in 
I  Hr.  per  Kg. 

Animal. 


2.905 
2. 151 
1.766 
1.540 

1-317 
1.273 

1-454 


Percentage  Change 

OF  CO2  FOR  Each  i° 

C.  Rise  in  Temp,  of 

Air. 


—2-33 


— 2.67 

— 0.71 
-1-2.82 


THE    REGULATION    OF   TEMPERATURE.  93 

It  is  evident  from  the  table  that  there  was  a  constant  de- 
crease in  the  metabolism  as  the  air  was  warmed  from  o°  to  35° 
C.  The  metabolism  at  0°  was  two  and  a  half  times  that  at  30°, 
an  increase  as  pronounced  as  is  incurred  as  the  result  of  severe 
muscular  work.  The  animal  at  0°  was  not  observed  to  move 
around  any  more  than  he  did  at  30°.  Other  experiments  con- 
firmed Rubner  in  the  view  that  the  critical  temperature,  or  the 
temperature  of  the  minimum  metabolism,  lay  at  33°.  At  this 
point  temperature  had  the  least  influence  on  total  metabolism. 
WTien  the  temperature  is  raised  from  30°  there  is  at  first  no 
increase  in  the  metabolism.  This  is  due  to  the  action  of  the 
apparatus  for  the  physical  regulation  of  body  temperature. 
As  the  temperature  rises  the  blood-vessels  of  the  skin  become 
dilated  and  the  evaporation  of  water  from  the  body  is  pro- 
moted. These  factors  tend  to  maintain  the  normal  tempera- 
ture of  the  organism  by  physical  means.  If  the  temperature  of 
the  air  be  high,  so  that  the  physical  regulation  be  not  sufficient 
to  cool  the  body,  then  a  supernormal  temperature  ensues.  Such 
a  febrile  temperature  raises  the  metabolism  by  warming  the 
cells,  as  is  seen  in  the  table  of  the  experiment  in  which  the 
guinea-pig  was  exposed  to  a  temperature  of  40°.  The  range  of 
the  physical  regulation — that  is,  the  period  during  which  external 
temperature  change  does  not  alter  metabolism — depends,  ac- 
cording to  Rubner,  on  the  natural  protections  which  an  animal 
possesses  which  insure  him  against  heat  loss.  These  are  two 
in  number — the  hairy  covering,  and  the  thickness  of  the  layer 
of  subcutaneous  fat. 

Rubner  has  shown  that  the  hair  of  the  black  cat,  black  lamb, 
rabbit,  skunk,  raccoon,  mink,  musk-deer,  and  sheep  is  of  itself 
relatively  light  in  weight,  but  that  the  fur  contains  a  very  large 
quantity  of  air.  The  whole  of  the  fur  covering  of  these  animals 
consists  of  between  97.3  and  98.8  per  cent,  of  air.  The  fur 
therefore  really  consists  of  air  with  between  1.2  and  2.7  per  cent, 
of  hair.  The  slight  conductivity  of  the  fur  is  principally  de- 
pendent on  this  layer  of  stationary  air.     If  an  animal  be  covered 


SCIENCE   OF   NUTRITION. 


with  a  fur  containing  this  stagnant  air,  he  will  be  better  protected 
from  loss  of  heat  than  if  he  had  none,  and  also  less  susceptible 
to  the  influence  of  cold  upon  the  surface  of  his  skin.  This  pro- 
tective covering  therefore  extends  the  range  of  the  physical 
regulation. 

Rubner^   gives  the  following  experiment  showing  the  in- 
fluence of  temperature  on  a  small  fasting  dog  with  long  hair: 

ACTION  OF  CHEMICAL  REGULATION  IN  THE  DOG. 


ist. 
2d. 

3d- 
4th 
5th 


2 

0 

I 

g' 

w 

< 

« 

M 

H 

s 

fa 

a 

fa 
a 

0 

;z; 

W 

y 

u 

0 

0 

u 

& 

pL, 

►J 

A 

& 

hj 

a 

R 

[4 

1-1 

s 

5 

0 

§ 

I 

g 

i 

< 

< 

% 

:z: 

H 

0 

u 

H 

u 

0 

U 

H 

i.8o 

0.06 

1.86 

20.0 

r.i 

21.0 

14.9 

46.5 

18,3.6 

230.1 

1.56 

0.06 

1.62 

22.4 

I.O 

23-4 

18.0 

40.4 

224.6 

264.6 

1.52 

0.06 

1.58 

28.2 

I.O 

29.1 

23-9 

39-5 

294.7 

334-2 

1.56 

0.06 

1.62 

18.9 

1.0 

19.9 

14-5 

40.5 

179.0 

219.5 

1.42 

0.06 

1.48 

17-3 

0.9 

18.2 

13-7 

37-0 

169.3 

206.3 

20.0"" 

15.2° 

7.6° 

30.0° 

25.2° 


One  observation  was  made  in  this  experiment  on  the  dog 
which  was  not  possible  in  the  case  of  the  guinea-pig,  and  that 
concerned  the  nitrogen  excretion.  The  nitrogen  excretion  for 
twenty-four  hours  is  not  increased  by  exposing  the  dog  to  a  tem- 
perature of  7.6°.  The  increased  metabolism  is  entirely  at  the 
expense  of  fat.  We  have  seen  that  this  may  also  be  true  of 
work  which  may  be  accomplished  at  the  expense  of  fat  without 
raising  the  protein  metabolism. 

Reduced  to  terms  of  calories  produced  per  kilogram  of  dog, 
the  following  results  are  obtained : 

Temperature.  Calories  per  Kilo. 

7.6° 86.4 

15-0° 63.0 

20.0° 55.9 

250° 54  2 

30.0° 56.2 

35-o° 68.5 

^Rubner:   "Die  Gesetze  des  Energieverbrauchs,"  1902,  p.  105. 


THE    REGULATION   OF   TEMPERATURE. 


95 


A  temperature  of  20°  was  readily  borne  by  this  dog  without 
any  increase  of  his  metabolism.  The  period  of  unchanging 
metabolism  extended  over  at  least  ten  degrees  between  20°  and 
30°,  during  which  time  the  physical  regulation  alone  sufhced 
to  maintain  evenly  the  body's  temperature.  At  35°  a  decided 
increase  of  heat  production  set  in,  on  account  of  the  warming 
of  the  cells  through  insufficient  heat  loss.  That  the  range  of 
the  physical  regulation  of  the  temperature  of  this  small  dog  was 
due  to  his  long  hair  is  shown  by  the  change  in  his  metabolism 
after  shaving  him.     Rubner  shows  this  in  the  following  table : 


Temperature. 

Calories  per  Kilo. 

Normal  Coat  of  Hair. 

Shaved. 

20° 

55-9 
54-2 
56.2 

82.3 

2!;° 

^0° 

52.0 

It  is  clearly  seen  that  this  dog  lost  his  power  of  physical 
regulation  between  20°  and  30°  as  soon  as  he  lost  his  covering 
of  hair.  His  metabolism  became  like  that  of  the  guinea-pig, 
increasing  with  a  reduction  of  temperature  from  30°  downward, 
an  illustration  of  chemical  regulation. 

E.  Voit^  shows  that  the  metabolism  of  a  pigeon  may  be 
doubled  after  removing  its  feathers. 

Babak^  finds  that  if  rabbits  are  shaved  and  varnished  with 
starch  paste  their  metabolism  rises  140  per  cent.,  which  in- 
crease maintains  their  body  temperature  at  the  normal  for 
several  weeks,  although  the  room  temperature  be  between  15° 
and  20°. 

To  determine  the  influence  of  the  second  factor,  that  of  the 
protecting  layer  of  fat,  Rubner^  investigated  the  influence  of 

'Voit:  " Sitzungsber.  der  Ges.  fiir  Morph.  u.  Physiol.,"  1904.  Bd.  xix,. 
P-  39- 

*Babak:  "Pfliiger's  Archlv,"  1905,  Bd.  cviii,  p.  389. 
'Rubner:  Ibid.,  1902,  p.  137. 


C)6  SCIENCE   OF  NUTRITION. 

temperature  on  the  metabolism  of  a  fasting  short-haired  dog^ 
at  a  time  when  he  was  emaciated,  and  compared  it  with  the 
fasting  metabohsm  after  the  same  dog  had  been  fattened.  The 
results  were  as  follows: 

Dog  (Thin).  Same  Dog  (Fat). 

Temperature.  Cal.  per  Kilo.  Temperature.  Cal.  per  Kilo 

S.i° 121.3  7-3° 120.5 

14-4° ..100.9  15.5° 83.0 

23.3° 70.7  22.0° 67.0 

30.6° 62.0  31.0° 64.5 

It  appears  from  the  above  that  the  metabolism  of  the  dog 
was  the  same  at  a  low  temperature  in  both  cases,  but  that  the 
minimum  metabolism  was  almost  reached  at  a  temperature  of 
22°  when  the  dog  had  a  protective  covering  of  fat,  which  was 
not  the  case  when  he  was  thin.  The  presence  of  adipose  tissue, 
therefore,  acts  in  the  same  way  as  does  a  warm  fur  to  extend  the 
range  of  the  physical  regulation,  and  to  delay  the  onset  of  the 
chemical  regulation  of  body  temperature. 

The  physical  regulation  may  be  increased  by  certain  volun- 
tary acts,  such  as  are  observed  when  a  dog  exposed  to  cold  lies 
down  and  curls  himself  up  in  such  a  way  as  to  offer  as  small  an 
exposed  surface  as  possible.  The  contrast  to  this  is  offered 
when  on  a  hot  day  the  dog  lies  on  his  back  and  extends  his  limbs 
so  as  to  promote  the  loss  of  heat. 

Rubner^  compared  the  fasting  metabolism  of  a  resting  dog 
exposed  to  air  at  about  18°  with  that  of  the  same  dog  quietly 
resting  suspended  in  a  net,  by  which  means  his  surface  was 
more  exposed  to  the  influence  of  cold.  The  results  were  as 
follows : 

Day  of        Cal.  from        Cal.  from 
Starvation.     Protein.  Fat.  Total.  Temp. 

Resting 2  33.79  430-91  464-7  17-5° 

Resting  in  net 3  33-79  581.50  615.2  18.2° 

Rubner'  also  cites  an  important  modification  of  metabolism 
through  a  variation  in  the  humidity  of  the  atmosphere. 

'Rubngr:    "Energiegesetze,"  1902,  p.  184. 
^  Rubner:   Ibid.,  1902,  p.  188. 


THE  REGULATION  OF  TEMPERATURE. 


97 


At  a  medium  temperature  during  fasting  (as  well  as  on  a 
medium  diet)  the  metabolism  of  a  dog  was  practically  unaffected 
by  an  increase  of  humidity  in  the  air,  as  appears  below: 

Cal.  in  Humidity  in 

Temperature  20.2°  24  Hours.  Per  Cent. 

Dr\-  day 258.4  34 

Humid  day 256.6  69 

More  on  dn'  day i  .8 

However,  on  a  liberal  diet  the  metabolism  increases  on  a  damp 
day  even  at  a  medium  temperature,  as  for  example : 

Cal.  in  Humidity  in 

Temper.\ture  20.2°  24  Hours.  Per  Cent. 

Ven'  dn-  day 249.4  13 

Humid  day 261.9  66 

More  on  humid  day 12.5 

The  increase  is  5  per  cent. 

On  a  very  hot  day  (on  a  moderate  fat  diet)  the  dog's  metab- 
olism is  increased  by  the  presence  of  moisture  in  the  atmos- 
phere. 

Temperature  35°. 

Calories  per  Kg.  Humidity  in  Per  Cent. 
69.28  9.1 

73-54  30-0 

Under  these  circumstances  the  metabolism  rose  6.1  per  cent,  in 
the  more  humid  air.  There  was  probably  an  overwarming  of 
the  cells,  on  account  of  the  difficulty  of  heat  loss  by  evaporation  of 
water.  A  cold,  damp  environment  of  0°  to  5°  temperature  also 
favors  an  increased  metabolism.  Rubner  attributes  this  action 
of  humidity  to  the  increased  conductivity  of  a  hair  covering  con- 
taining moisture,  and  says  that  this  loss  may  be  partially  bal- 
anced by  a  decreased  evaporation  of  water  from  the  lungs. 

The  metabolism  and  the  manner  of  heat  loss  may  therefore 
be  variously  affected  by  the  condition  of  the  atmosphere  as  re- 
gards moisture. 

On  days  of  ordinary  dryness  Rubner*  calculates  the  foUow- 

'  Rubner:   "Energiegesetze,"  1902,  p.  189. 
7 


98 


SCIENCE   OF  NUTRITION. 


ing  division  of  the  heat  loss  in  a  starving  dog  under  the  influence 
of  different  temperatures: 

INFLUENCE  OF  TEMPERATURE  ON  MANNER  OF  HEAT  LOSS. 


Temperature. 

Calories  Lost  by 

Conduction  and 

Radiation. 

Calories  Lost  by 

Evaporation  of 

Water. 

Total  Calories 
of  Metabolism. 

Humidity 

IN  PER  Cent. 

7° 

78-S 
55-3 
45-3 
41.0 

33-2 

7-9 

7-7 

10.6 

13.2 

23.0 

86.4 
63.0 

55-9 
54-2 
56.2 

24 
34 
29 
19 
14 

1.;° 

20°      

2C°         

:!0° 

It  is  clear  that  at  7°  only  a  little  heat  is  lost  by  the  evaporation 
of  water  and  the  greater  part  by  conduction  and  radiation.  As 
the  surrounding  air  becomes  warmer  the  power  to  lose  heat  by 
radiation  and  conduction  diminishes  and  the  loss  through  the 
evaporation  of  water  increases. 

Rubner  has  charted  this  experiment  after  making  allow- 
ances^ for  the  varying  moisture  conditions.  The  chart  is  repro- 
duced on  p.  99.  The  chart  epitomizes  the  method  of  heat  loss 
in  a  starving  dog  under  the  influence  of  varying  temperatures. 

The  discussion  of  the  metabolism  has  given  a  foundation  for 
the  understanding  of  the  basic  requirement  of  an  organism. 
The  minimum  requirement  for  energy  is  seen  to  be  present 
when  the  fasting  organism  is  surrounded  by  an  atmosphere 
having  a  temperature  of  30°  to  35°.  This  may  be  called  the 
hasal  requirement,  the  minimum  of  energy  compatible  with  cell 
life.  This  basal  requirement  is  modified  by  temperature,  by 
food,  and  by  work,  and  it  is  an  important  factor  to  keep  in  mind 
(see  p.  210). 

The  principles  laid  down  here  regarding  the  lower  animals 
apply  equally  to  man.  He  too  may  come  under  the  influence 
of  chemical  regulation,  although  he  constantly  endeavors  to 
maintain  the  surface  of  his  skin  at  a  tropical  temperature  through 
the  use  of  clothes.     His  heat  loss  may,  like  the  dog's,  be  more 

^Rubner:   "Archiv  fur  Hygiene,"  1891,  Bd.  xi,  p.  208. 


THE   REGtTLATION   OF   TEMPERATURE. 


99 


difficult  if  he  be  covered  with  a  thick  layer  of  fat.  And  his 
metabolism  is  also  influenced  by  atmospheric  conditions  of 
moisture,  wind,  and  temperature. 

One  of  the  earliest  demonstrations  of  the  action  of  chemical 
regulation  was  afforded  by  Voit,  who  placed  a  fasting  man 


l^^r  kilogram. 

Fig.  4. — Rubner's  chart  showing  the  manner  of  heat  loss  at  different  room 
temperatures  in  the  dog.  Blue,  Heat  loss  in  calories  through  evaporation  of 
water.     Red,  Heat  loss  in  calories  through  radiation  and  conduction. 

The  distance  between  opposite  points  of  the  curved  line  represents  the  total 
metabolism  at  a  particular  temperature. 


weighing  70  kilograms  in  the  Pettenkofer-Voit  respiration  ap- 
paratus and  determined  the  carbon  dioxid  and  nitrogen  output 
for  six  hours.  The  person  accustomed  himself  to  the  given 
temperature  by  staying  under  its  influence  for  some  time  previous 
to  the  commencement  of  the  experiment.  In  the  cold  experi- 
ments the  ventilating  air  was  derived  from  the  winter  atmos- 


lOO  SCIENCE   OF  NUTRITION. 

phere.  For  the  warm  periods  the  air  was  artificially  heated. 
The  subject  of  the  experiment  wore  clothing  which  was  com- 
fortable in  the  usual  warm  atmosphere  of  the  laboratory.  Voit^ 
gives  the  following  results: 

EFFECT  OF  TEMPERATURE  ON  THE  METABOLISM  OF  A  FASTING 
MAN.     SIX-HOUR  PERIODS. 

COa  Excreted  N  in  Urine 

Temperature.  in  G.  in  G. 

4-4° 210.7  4-23 

6.5° 206.0  4.05 

9.0° 192.0  4.20 

14-3° I55-I  3-8i 

16.2° 158.3  4.00 

23-7° 164.8  3.40 

24-2° 166.5  3.34 

26.7° 160.0  3.97 

30.0° 170.6 

The  nitrogen  elimination  remains  unaffected  by  temperature. 
At  the  ordinary  room  temperature  there  scarcely  seems  to  be 
any  increase  in  carbon  dioxid  output,  but  at  the  lower  temper- 
atures the  quantity  of  the  fat  metabolism  is  markedly  increased, 
as  shown  by  the  rise  of  carbon  dioxid  elimination.  The  in- 
dividual sat  quietly  in  a  chair,  but  at  a  temperature  of  4.4° 
could  not  prevent  himself  from  shivering. 

The  whole  effect  of  the  chemical  regulation  in  man  has  been 
attributed  by  Johansson^  to  the  additional  metabolism  due  to 
shivering.  Voit  did  not  believe  that  this  could  be  the  cause, 
nor  that  the  increased  respiratory  activity  could  account  for  the 
rise  in  metabolism.  Voit  believed  the  increase  to  be  a  reflex 
stimulus  of  cold  on  the  skin  which  raised  the  power  of  the 
muscle  cells  to  metabolize.  Voit's  views  have  been  confirmed  in 
Rubner's  laboratory^  in  the  following  series  of  experiments  on 
a  man: 

Temperature.  CO2  in  Grams  per  Hour. 

^5 32  3 

20° 30.0 

23° 27.9 

'K 317 

29° 32.4 

^  Voit:   "Zeitschrift  fiir  Biologie,"  1878,  Bd.  xiv,  p.  80. 

^Johansson:  "Skan.  Archiv  fiir  Physiologie,"  1896,  Bd.  vii,  p.  123. 

^Rubner:   "Energiegesetze,"  1902,  p.  203. 


THE  REGULATION  OF  TEMPERATURE.  lOI 

In  this  experiment  there  was  no  shivering  at  a  temperature 
of  15°  and  yet  the  metaboHsm  increased  from  what  it  was  at  23°. 

It  has  also  been  shown  that  cool  baths  and  winds  increase 
the  metabolism,  which  must  be  effected  through  the  chemical 
regulation.  Lefevre^  states  that  a  man,  who  has  been  inured 
to  it,  may  sit  naked  for  several  hours  in  a  cold  wind  without  a 
reduction  of  body  temperature. 

Rubner^  has  measured  the  effect  of  baths  and  douches  last- 
ing three  and  a  half  to  five  minutes.  When  the  water  has  a  tem- 
perature of  16°  he  finds  that  the  carbon  dioxid  elimination  may 
be  very  largely  increased,  especially  in  the  case  of  the  douche. 
The  effect  of  the  douche  was  more  marked  if  taken  before 
breakfast  when  the  intestinal  tract  is  free  from  food.  The 
results  before  breakfast  were  as  follows : 

INFLUENCE   OF   COLD   BATHS   ON   METABOLISM   IN   MAN. 


Volume  of  respiration. . 
Carbon  dioxid  excreted. 
Oxygen  absorbed 


Douche  i6°.    In- 
crease IN  PER 
Cent. 


54-5 
149-5 

IIO.I 


Bath  i6°.     In- 
crease IN  per 
Cent. 


22.9 
64.8 
46.8 


A  cold  bath,  especially  a  douche,  will  therefore  stimulate 
to  a  greatly  increased  metabolism.  The  mechanical  stimulus  of 
the  falling  cold  water  apparently  acts  reflexly  to  increase  the 
metabolism  greatly,  as  it  certainly  does  the  magnitude  of  the 
respiration.  The  respiratory  quotient  indicates  that  the  in- 
creased metabolism  is  at  the  expense  of  the  glycogen  supply. 
There  is  an  after-effect  which  lasts  about  one  and  a  half  hours, 
indicating  an  increased  metabolism  during  that  time.  This 
may  be  the  expression  of  the  body's  attempt  to  maintain  a 
normal  temperature  after  being  .somewhat  cooled  (see  also  p.  318). 

It  is  obvious  that  a  cold  bath  will  be  likely  to  induce  shiver- 

'Lefevrc:   "Comptes  rendus,"  1894,  p.  604. 

'  Rubner:   "  Archiv  fur  Hygiene,"  1903,  Bd.  xlvi,  p.  390. 


I02 


SCIENCE   OF  NUTEITION. 


ing  unless  by  mechanical  effort,  such  as  swimming,  the  metabo- 
lism is  increased  so  as  to  supply  calorific  energy  in  another 
way  than  through  chemical  regulation  (see  p.  193). 

A  bath  of  35°  has  no  effect  on  metabolism. 

Rubner  finds  that  a  bath  at  44°  again  increases  the  metabo- 
lism, the  increase  being,  for  the  volume  of  respiration,  18.8  per 
cent.,  for  carbon  dioxid  32.1  per  cent.,  and  for  oxygen  17.3  per 
cent.  This  is  probably  due  to  the  overwarming  of  the  cells. 
Baths  at  this  temperature  find  favor  among  the  Japanese. 

The  effect  of  wind  is  such  that  an  imperceptible  air  current 
may  have  a  very  pronounced  effect.  Rubner^  has  shown  that 
wind  becomes  perceptible  when  it  attains  a  velocity  of  0.4  to 
0.5  meter  a  second,  and  that  if  a  wind  much  below  this  threshold 
value,  having  a  velocity  of  0.18  meter  per  second,  act  upon  the 
exposed  area  of  the  arm,  there  is  an  increased  heat  loss  of  be- 
tween 19  and  75  per  cent.,  depending  on  the  temperature  of  the 
wind,  above  what  would  be  lost  were  the  air  quiet. 

The  effect  of  wind  of  moderate  humidity  and  different  tem- 
peratures on  the  metabolism  of  a  man  clad  in  summer  clothes, 
as  compared  w^ith  the  metabolism  during  atmospheric  calm,  is 
shown  in  Wolpert's^  experiment  below: 

INFLUENCE  OF  WIND  ON  METABOLISM  IN  MAN. 


Temperature. 


Calm. 


Grams  CO2  per 
Hour. 


Wind  r  Meter 
PER  Second. 


Grams  CO2  per 
Hour. 


Wind  8  Meters 
PER  Second. 


Grams  CO2  per 
Hour. 


10-15' 
15-20' 
20-25' 
25-30' 
30-35' 
35-40' 


29.8 
25.1 
24.1 
25.0 
25-3 
23-7 


28 


30.0 
30.1 
28.0 
24.4 
21.6 


^Rubner:   "Archiv  fiir  Hygiene,"  1904,  Bd.  1,  p.  296. 
^Wolpert:  Ibid.,  1898,  Bd.  xxxiii,  p.  206. 


THE  REGULATION  OF  TEMPERATURE. 


103 


According  to  this,  a  breeze  having  a  temperature  of  15°  to  20° 
and  moving  at  the  rate  of  about  15  miles  per  hour  (8  meters  per 
second)  has  a  greater  effect  upon  the  metabolism  of  a  man  clad 
in  summer  clothing  than  a  temperature  of  2°  would  have  during 
perfect  atmospheric  quiet.  In  all  the  experiments  the  smallest 
amount  of  carbon  dioxid  is  eliminated  between  30°  and  40°. 

The  above  experiments  were  performed  on  a  thin  man,  and 
it  will  be  noticed  that  there  was  no  rise  in  his  metabolism  at  a 
temperature  of  between  35°  and  40°.  Rubner  explains  this  as 
due  to  the  sufficiency  of  the  evaporation  of  perspiration  on  the 
surface  for  the  cooling  of  the  organism. 

A  fat  man,  however,  with  a  thick,  ill-conducting  layer  of 
adipose  tissue,  is  not  so  immune  to  the  effect  of  high  tempera- 
tures upon  his  metabolism.  This  is  especially  pronounced  in 
a  damp  climate.  Thus  Rubner^  obtains  the  following  results 
from  a  fat  man  wearing  clothes: 


INFLUENCE  OF  TEMPERATURE  AND  HUMIDITY  ON  THE  ME- 
TABOLISM OF  A  FAT  MAN. 


Temperature. 


20" 

28-30° 

36-37° 


Humidity  30  per  Cent. 


CO2  in  grams 
per  hour. 


33-7 
36.9' 


42. 6^ 


H2O  evap- 
orated per 
hour. 


56 
134 


204 

+  14  g- 
sweat. 


Humidity  60  per  Cent. 


CO2  in  grams 
per  hour. 


30-7 
44-S' 


46.7* 


H2O  evapor- 
ated per  hour. 


17 

170-1- 

31  g- 
sweat. 
186 

+  255  g- 
sweat. 


'  Body  temperature  rose  0.1° 

2        11  11  11        Q^O 


3  Body  temperature  rose  0.4° 
*    "  "  "    0.9° 


The  fact  that  in  the  experiment  where  there  was  30  per  cent, 
humidity  the  metabolism  largely  increased  at  36°  to  37°  without 
concomitant  rise  in  body  temperature,  leads  Rubner  to  theorize 
that  there  must  have  been  an  overheating  of  the  cells  where  the 

'Rubner:   "Encrgicgesctzc,"  1902,  pp.  208,  232. 


I04  SCIENCE   OF  NUTRITION. 

metabolism  was  progressing,  even  though  this  might  not  have 
been  determinable  by  the  clinical  thermometer. 

It  appears  that  on  a  hot,  humid  day  the  metabolism  of  a  fat 
individual  may  be  fifty  per  cent,  higher  than  on  a  day  of  moder- 
ate temperature  and  the  same  humidity.  The  whole  of  the 
body  heat  is  lost  through  the  evaporation  of  water  which  is  here 
hindered  by  the  humidity.  There  is  a  large  and  exhausting 
excretion  of  sweat  which  on  account  of  the  difficulty  in  evapora- 
tion is  not  effective  in  cooling  the  body.  At  a  moderate  tem- 
perature, where  the  greater  part  of  the  heat  loss  is  by  radiation 
and  conduction,  the  excretion  of  water  is  not  excessive. 

There  can  be  no  doubt  that  climatic  conditions  modify 
racial  characteristics.  The  emigrant  from  northern  Europe, 
living  upon  a  farm  in  the  hot  and  often  moist  climate  of  an  Amer- 
ican summer,  must  restrict  his  layer  of  adipose  tissue  if  he  is  to 
live  comfortably.  The  same  holds  true  in  Italy.  The  difference 
between  John  Bull  and  Uncle  Sam  seems  to  be  one  of  climatic 
adaptation.  On  the  contrary,  the  Eskimo  cultivates  a  thick,  fat 
layer  to  protect  himself  from  frost.  It  is  also  interesting  to  note 
that  prostrations  from  the  heat  appear  in  New  York  with  66 
per  cent,  humidity  and  a  temperature  of  31.5°  (2.30  p.m., 
August  24,  1905).  Rubner^  says  that  a  lightly  clad  thin  man, 
at  a  temperature  of  30°  with  humidity  at  65  per  cent.,  bore  the 
effect  so  badly  that  he  feared  to  raise  the  temperature  to  35°. 
This  individual  had  readily  tolerated  35°  in  dry  air. 

The  maximum  mortality  from  "summer  troubles"  in  chil- 
dren in  New  York  coincides  with  the  first  great  wave  of  heat 
accompanied  by  humidity  which  falls  upon  the  city.  Similar 
climatic  conditions  at  later  dates  are  not  so  fatal.  It  may  be 
that  the  fatality  of  these  intestinal  affections  is  due  to  the  inef- 
ficiency of  the  apparatus  for  the  physical  discharge  of  heat  in 
the  infant  organism.  It  is  also  possible  that  infection  may  be 
more  readily  achieved  under  these  conditions  (p.  217). 

Another  factor  in  the  heat  regulation  of  man  is  clothes. 

^Rubner:   "Energiegesetze,"  1902,  p.  232. 


THE   REGULATION   OF   TEMPERATURE. 


105 


Certain  savage  races  living  in  cool  climates  do  without  clothes, 
as,  for  example,  natives  of  Terra  del  Fuego,  who  substitute  a 
covering  of  oil.  In  such  races  the  process  of  "hardening"  or 
the  development  of  the  physical  regulation  must  be  carried  to  a 
maximum.  In  civilized  countries  man  endeavors  to  remove  all 
the  influence  of  chemical  regulation  by  keeping  his  skin  covered. 
Only  about  20  per  cent,  of  his  surface  is  normally  exposed  to  the 
air.  The  most  important  constituent  of  clothes  is  the  air,  which 
is  a  much  worse  conductor  of  heat  than  is  the  fiber.  This  is 
especially  true  of  furs  (p.  93).  Thickness  of  the  cloth  will  give 
a  greater  layer  of  air  and  will  prevent  heat  loss  from  the  body. 
A  densely  woven  cloth  prevents  proper  ventilation  and  does  not 
absorb  moisture.  In  hot  weather  a  porous  cloth  next  to  the 
skin  which  can  absorb  moisture  and  permit  its  ready  evaporation 
is  of  high  importance.  If  a  garment  worn  next  to  the  skin 
become  thoroughly  wet  the  evaporation  of  sweat  at  a  high 
temperature  is  largely  prevented,  to  the  great  discomfort  of 
the  individual,  while  at  a  lower  temperature  heat  loss  through 
conduction  is  greatly  facilitated,  with  a  sensation  of  chill.  Two 
experiments  cited  by  Rubner^  indicate  the  effect  of  clothes  on 
metabolism.  An  individual  was  kept  at  a  temperature  of 
between  11°  and  12°  and  wore  different  clothes  at  different 
times.     His  carbon  dioxid  and  water  excretion  were  as  follows: 


INFLUENCE  OF  CLOTHES  ON  METABOLISM  IN  MAN  AT  A  TEM- 
PERATURE OF  11°  to  12°. 

CO2  IN  Grams 
PER  Hour. 

H2O  m  Grams 
per  Hour. 

Remarks. 

Summer  clothes 

28.4 

26.9 
23.6 

58 
63 

Cold,  occasional  shiv- 

Summer clothes  and  winter 
overcoat  

ering. 
Chilly  part  of  the  time. 
Comfortably  warm. 

Summer    clothes   and    fur 
coat 

'Rubner:  " Energiegesetze,"  1902,  p.  225. 


Io6  SCIENCE   OF  NUTRITION. 

When  the  man  was  comfortable  the  chemical  regulation  of 
temperature  was  eliminated. 

Rubner  remarks  that  while  the  radiant  energy  of  the  sun 
is  large  in  quantity,  he  has  been  unable  to  find  any  influence 
upon  a  man  under  ordinary  circumstances,  but  believes  that  it 
may  take  the  place  of  heat  produced  through  chemical  regulation 
on  cold  days.  Thus  a  person  living  in  the  high  altitude  of  Davos, 
Switzerland,  feels  much  more  comfortable  in  the  sun  on  a  cold 
day  than  he  does  in  the  shade.  However,  Zuntz  while  living 
on  the  summit  of  Monte  Rosa  found  that  sunlight  did  not 
reduce  metabolism  (p.  260), 

In  what  follows  it  will  be  shown  that  the  ingestion  of  food 
,may  add  to  the  heat  production  of  the  organism  and  diminish 
the  necessity  of  heat  production  through  chemical  regulation  in 
cold  weather.  Also,  it  may  very  uncomfortably  increase  the 
production  of  heat  and  perspiration  in  warm  weather,  especially 
if  protein  be  largely  taken  (p.  217). 

From  this  chapter  the  influence  of  climate  is  seen  to  be  note- 
worthy. It  explains  why  a  temperature  of  — 40°  may  be  com- 
fortably borne  in  winter,  in  the  Adirondacks,  for  example,  if 
the  air  be  dry  and  still ;  why  a  much  warmer  atmosphere  which 
is  damp  and  windy  may  "cut  to  the  bone"  with  cold;  why  a 
hot,  dry  climate  may  be  entirely  comfortable,  when  air  at  the 
same  temperature  laden  with  moisture  may  strike  down  many 
fatally  and  oppress  every  one;  and  how  the  effect  of  heat  may 
be  modified  by  the  breezes  and  baths  at  the  seashore.  It  does 
not  explain  the  effect  of  the  dry  sirocco  wind  which  blows  from 
the  Desert  of  Sahara,  the  universal  depressant  action  of  which 
has  been  attributed  to  unknown  cosmic  influences. 


CHAPTER  IV. 

THE  INFLUENCE  OF  PROTEIN  FOOD. 

PART  ONE. 

It  has  been  thought  that  protein  is  a  food  which  is  in 
itself  sufficient  for  all  the  requirements  of  the  body.  Pfliiger^ 
was  able  to  keep  a  very  thin  dog  in  good  condition  and  doing 
active  exercise  during  a  period  of  seven  months,  the  sole  diet 
being  meat  cut  as  free  from  fat  as  possible.  Pfiiiger  says  that 
the  fat  and  glycogen  content  of  the  meat  ingested  could  not  have 
yielded  sufficient  energy  to  provide  for  the  action  of  the  heart 
alone.  It  must  be  remembered,  however,  that  meat  is  not  pure 
protein  but  is  mixed  with  salts  and  water.  The  simplest  diet 
capable  of  maintaining  the  body  in  condition  is  therefore  a  mix- 
ture of  materials,  or  foodstuffs.  Such  a  mixture  of  foodstuffs 
is  called  a  food.  A  foodstuff  is  a  material  capable  of  being 
added  to  the  body's  substance,  or  one  which  when  absorbed  into 
the  blood-stream  will  prevent  or  reduce  the  wasting  of  a  neces- 
sary constituent  of  the  organism. 
The  foodstuffs  are : 

Proteins  (including  albuminoids). 

Carbohydrates. 

Fats. 

Salts. 

Water. 
A  food  is  a  palatable  mixture  of  foodstuffs  which  is  capable 
of  maintaining  the  body  in  an  equilibrium  of  substance,  or  ca- 
pable of  bringing  it  to  a  desired  condition  of  substance.  The 
ideal  food  is  a  palatable  mixture  of  foodstuffs  arranged  together 
in  such  proportion  as  to  burden  the  organism  with  a  minimum  of 
labor.     These  definitions  are  Voit's.^ 

■PnUger:   "Pfliiger's  Archiv,"  1891,  Bd.  1,  p.  98. 
*  Voit:  Hermann's  Handbuch,  "StofTwcchsel,"  1881,  pp.  330,  344. 

107 


lo8  SCIENCE  OF  NUTRITION. 

If,  instead  of  natural  foods,  purified  materials  such  as  casein, 
egg  albumin,  vitellin,  potato  starch,  wheat  starch,  and  oleo- 
margarine together  with  the  proper  salts  be  mixed  and  given  to 
mice,  it  has  been  shown  by  Rohmann^  that  the  offspring  are  difi&- 
cult  to  rear  on  the  same  food,  and  no  living  young  can  be  ob- 
tained from  them.  Artificial  foods  will  therefore  not  replace 
the  natural  products.  Commercial  preparations  of  meat  are  not 
so  digestible  as  meat  itself.^ 

When  protein  alone  is  ingested  by  a  normal  adult  it  is  very 
readily  oxidized,  and  is  only  with  the  greatest  difficulty  deposited 
so  as  to  form  new  tissue  in  the  organism. 

In  the  early  experiments  of  Bischoff  and  Voit,  the  fact  is 
recorded  that  a  dog  weighing  35  kilograms  may  excrete  12 
grams  of  urea  in  twenty-four  hours,  and  the  same  dog  after 
receiving  2500  grams  of  meat  may  excrete  184  grams,  fifteen 
times  as  much. 

Voit^  has  shown  that  if  that  quantity  of  meat  be  administered 
which  corresponds  to  what  is  oxidized  in  starvation,  nitrogen 
equilibrium  will  not  be  established,  but  some  of  the  body's 
flesh  will  also  be  metabolized.  This  latter  quantity  grows 
steadily  less  if  the  amount  of  meat  ingested  be  gradually  in- 
creased until  finally  the  point  of  nitrogen  equilibrium  is  reached, 
at  which  the  amount  of  meat  ingested  is  equal  to  that  destroyed 
in  the  body.  To  illustrate  this  Voit  gives  the  following  table, 
the  results  of  work  done  on  a  dog: 


Grams  Meat 

Grams  Flesh 

Change 

Administered. 

Destroyed. 

IN  THE  Body. 

0 

233 

—233 

0 

190 

— 190 

300 

379 

—79 

600 

665 

-65 

900 

941 

—41 

1200 

1180 

-I-20 

1500 

1446 

+  54 

Nitrogen  equilibrium  was  not  reached  until  1200  grams  of  meat  were  given, 
or  about  five  times  the  amount  of  the  fasting  protein  metabolism. 

^Rohmann:   "Klinischer  therapeutisc"he  Wochenschrift,"  1902,  No.  40. 
^Poda  and  Prausnitz:    "Zeitschrift  fiir  Biologie,"  1901,  Bd.  xlii,  p.  377. 
^Voit:  Loc.  cit.,  1881,  p.  106. 


THE  INFLUENCE  OF  PROTEIN  FOOD,  1 09 

The  above  experiments  were  made  in  1858.  It  is  no  longer 
customary  to  calculate  the  protein  metabolism  in  terms  of  flesh 
destroyed,  but  in  terms  of  nitrogen.  The  old-fashioned  term 
flesh  meant  meat  with  a  nitrogen  content  of  3.4  per  cent.  It 
served  to  illuminate  the  significance  of  metabolism  at  a  time  when 
few  were  instructed  in  this  field  of  work. 

E.  Voit  and  Korkunoff^  have  published  a  research  of  sim- 
ilar character.  They  fed  a  dog  with  meat  which  had  been  treated 
with  lukewarm  water  to  remove  the  extractives,  and  which  was 
then  squeezed  in  a  press.  This  process  removes  most  of  the 
nitrogen- containing  substances  other  than  protein.  A  dog  will 
readily  eat  this  washed  meat  or  "protein."  The  idea  was  to 
determine  the  minimum  quantity  of  protein  which  it  was  pos- 
sible to  ingest  and  still  maintain  nitrogen  equilibrium.  The 
dift'erent  quantities  of  meat  tabulated  below  were  given  con- 
tinuously for  two  or  three  days  at  a  time.  Only  the  results  of 
the  last  day  of  each  of  these  periods  are  quoted: 

Food.  N  in  Food.     N  in  Excreta.      Difference. 

Starvation o 

100  g.  meat 4.10 


140  g. 
165  g- 
185  g. 
200  g. 

23°  g- 
360  g- 
410  g. 
360  g. 
Starvation 


third  dav. 


•  5-74 

•  6.77 
■  7-59 
.  8.20 
.10.24 
.ii.gg 

■15-58 
.13.68 


3-996 

—3-996 

s-558 

—1.458 

6.495 

— 0-75S 

7.217 

—0.447 

7.804 

-0.214 

8.726 

^.526 

10-579 

—0-339 

12.052 

— 0.062 

14-314  ■ 

-1-1.266 

13.622 

-1-0.058 

4.026 

— 4.026 

The  figures  show  that  nitrogen  equilibrium  was  reached 
only  after  supplying  three  and  a  half  times  the  amount  of  protein 
metabolized  in  starvation.  The  authors  calculate  that  at  this 
time  of  nitrogen  equilibrium  the  dog  was  still  losing  28  grams 
of  body  fat,  and  that  not  much  more  than  fifty  per  cent,  of  the 
total  energy  liberated  in  the  organism  was  furnished  by  the  pro- 
tein metabolism  of  the  time.  One  may  thus  have  nitrogen 
equilibrium  without  having  carbon  equilibrium. 

'E.  Voit  and  Korkunoff:  "Zeitschrift  fiir  Biologic,"  1895,  Bd.  xxxii,  p.  58. 


no 


SCIENCE   OF  NUTRITION. 


Systems  of  diet  for  fat  people  are  based  on  this  knowledge. 
A  loss  of  protein  is  highly  undesirable,  while  a  gradual  loss  of 
adipose  tissue  may  be  a  great  relief  to  the  obese. 

Bornstein^  finds  that  during  a  period  of  thirteen  days  he 
can  add  8.3  grams  of  protein  to  his  body  and  oxidize  90  grams  of 
body  fat  daily,  when  ingesting  a  mixed  diet  containing  1600 
calories  with  118  grams  of  protein.  Such  a  diet  contains  a 
fuel  value  less  than  the  requirement  of  his  organism  (p.  182). 

If  the  quantity  of  meat  ingested  be  steadily  increased  after 
nitrogenous  equilibrium  has  been  reached,  the  protein  metabo- 
lism will  gradually  increase,  nitrogenous  equilibrium  will  be 
established  at  higher  and  higher  levels,  and  there  will  be  a  cor- 
responding diminution  in  the  amount  of  fat  burned.  This  was 
shown  in  the  following  experiment  of  Voit,^  who  gave  different 
quantities  of  meat  to  a  large  dog  weighing  30  kilograms. 

INFLUENCE  OF  INGESTING  INCREASING  QUANTITIES  OF  MEAT. 
Weights  are  in  Grams. 


Meat  Ingested. 


500 
1000 
1500 
1800 
2000 
2500 


Flesh 
Destroyed. 


165 

599 

1079 

1500 

1757 
2044 
2512 


Gain  or  Loss  of 
Body  Flesh. 


-165 

—99 

—79 

o 

+  43 
—44 


Gain  or  Loss 
op  Body  Fat. 


—95 
—47 
—19 

+  4 

-l-i 

+  58 

+  57 


Respiratory 
Quotient. 


.76 

•74 
.81 


Nitrogen  equilibrium  existed  after  the  ingestion  of  1500  grams 
of  meat  and  there  was  also  no  loss  of  body  fat  (carbon  equilib- 
rium). When  2000  grams  and  even  2500  grams  of  meat  were 
supplied  it  was  all  destroyed,  as  was  indicated  by  the  amount  of 
nitrogen  in  the  urine,  but  a  certain  quantity  of  carbon  belonging 
to  the  ingested  protein  was  not  eliminated  in  the  respiration 
but  was  retained  in  the  body.  This  carbon  Pettenkofer  and 
Voit  believed  to  have  been  laid  up  in  the  body  in  the  form  of  fat. 

^Bornstein:    "Berliner  klinische  Wochenschrift,"  1904,   No.   46. 
^'Voit:   "Stoffwechsel,"  1881,  p.  117. 


THE   INFLUENCE    OF    PROTEIN   FOOD.  II i 

The  respiratory  quotient  in  the  foregoing  series  gradually 
rises,  as  would  be  expected  from  the  increasing  prominence 
of  the  protein  in  the  metabolism  (p.  28).  Meat  alone  will 
therefore  support  a  dog.  Rubner^  says  that  a  man  cannot  live 
on  meat  alone,  not  because  the  intestinal  canal  cannot  digest  it, 
but  because  of  the  physical  limitations  of  the  apparatus  of  mas- 
tication. 

A  subject  of  interest  in  considering  the  value  of  protein  in 
metabolism  is  that  of  the  value  of  gelatin.  Gelatin  is  an  artifi- 
cial derivative  of  collagen,  an  albuminoid  largely  found  in  the 
skeletal  structure  of  animals.  Gelatin  contains  very  nearly 
the  same  quantity  of  nitrogen  as  protein;  it  breaks  up  on  chemi- 
cal treatment  into  the  same  amino-acids,  except  that  it  does  not 
yield  tyrosin,  cystin,  and  tryptophan.  In  the  diabetic,  gelatin 
yields  the  same  amount  of  sugar  as  does,  protein.^  To  what 
extent  gelatin  may  take  the  place  of  protein  in  the  body's  metab- 
olism has  long  been  the  subject  of  inquiry. 

It  was  shown  first  by  Bischoff  and  VoitHhat  no  matter  how 
much  gelatin  was  ingested  it  was  always  completely  burned  and 
some  of  the  body's  protein  in  addition.  Therefore  gelatin  never 
builds  up  new  tissue,  although  it  may  somewhat  diminish  tissue 
waste.  Gelatin  may  be  formed  from  protein  in  the  body,  but 
it  cannot  be  reconverted  into  protein  nor  act  like  protein  in 
metabolism,  Kirchmann,*  working  in  the  laboratory  of  Erwin 
Voit,  has  sho\Mi  to  what  extent  gelatin  spares  protein  in  metabo- 
lism. If  one  takes  the  amount  of  protein  metabolism  in  starva- 
tion as  one,  then  the  ingestion  of  about  the  same  quantity  of 
gelatin  reduces  the  body's  protein  waste  23  per  cent.,  and  if 
eight  times  this  amount  of  gelatin  be  given,  the  tissue  waste  may 
be  reduced  35  per  cent.     In  other  words,  the  ingestion  of  7.5 

*  Rubner:  von  Lcydcn's  "Ilandbuch  der  Ernahrungsthcrapic,"  1903,  Bd. 
i,  p.  42. 

^Reilly,  Nolan,  and  Lusk:  "American  Journal  of  Physiology,"  1898,  vol.  i, 
P-  395- 

*  Voit:  Hermann's  Handbuch,  "Stoffwechsel,"  1881,  p.  396. 
*Kirchmann:   "Zcitschrift  fur  Biologie,"  1900,  Bd.  xl,  p.  54. 


112  SCIENCE   OF  NUTRITION. 

per  cent,  of  the  total  heat  requirement  of  the  organism  in  the 
form  of  gelatin  spares  23  per  cent,  of  the  body's  protein,  while 
the  ingestion  of  60  per  cent,  of  the  requirement  will  only  cause 
a  decrease  of  35  per  cent,  in  protein  waste.  Krummacher^ 
showed  that  the  ingestion  of  the  full  heat  requirement  of  the 
animal  in  the  form  of  gelatin  reduced  the  fasting  protein  metab- 
olism by  only  37.5  per  cent.  -  It  is  evident  that  no  matter  how 
much  gelatin  be  given,  tissue  protein  continues  to  be  destroyed, 
and  it  is  also  evident  that  a  small  quantity  of  gelatin  has  almost 
as  great  an  effect  as  a  large  quantity. 

An  extremely  interesting  experiment  of  Kauffmann^  shows 
that  when  the  lacking  tyrosin,  cystin,  and  tryptophan  are  mixed 
with  gelatin  in  the  proportions  in  which  they  occur  in  true  pro- 
tein, and  are  given  to  a  dog  or  to  a  man,  nitrogen  equilibrium 
may  be  established. 

It  is  evident  from  this  experiment  that  the  value  of  the  var- 
ious proteins  in  nutrition  may  depend  upon  their  constituent 
amino-acids,  and  for  this  reason  the  table  on  p.  113  of  the  com- 
position of  vegetable  and  animal  proteins  as  furnished  by  the 
fundamentally  valuable  work  of  Osborne  and  of  Abderhalden 
has  been  compiled. 

Concerning  the  crystalline  vegetable  proteins  which  he  has 
investigated  Osborne^  writes:  "It  is  possible  to  establish  a  con- 
stancy of  properties  and  ultimate  composition  between  succes- 
sive fractional  precipitations  which  give  no  reasons  for  believing 
the  substance  to  be  a  mixture  of  two  or  more  individuals. 
On  chemical  grounds  there  is  no  more  reason  for  dividing  the 
proteins  into  two  groups  of  animal  and  vegetable  proteins  than 
there  is  in  making  a  similar  distinction  between  the  carbohy- 
drates. Of  twenty-three  seed  proteins  which  have  been  hy- 
drolized  all  have  yielded  leucin,  prolin,  phenylalanin,  aspartic 
acid,  glutamic  acid,   tyrosin,  histidin,   arginin  and  ammonia. 

^  Krummacher:  Ibid.,  1901,  Bd.  xlii,  p.  242. 

^  Kauffmann:  "Pfluger's  Archiv,"  1905,  Bd.  cix,  p.  440. 

'Osborne:   "Science,"  1908,  vol.  xxviii,  p.  417. 


THE  INFLUENCE  OF  PROTEIN  FOOD. 


113 


Glycocoll,  lysin,  and  tryptophan  are  the  only  amino-acids  which 
have  been  proved  lacking  in  any  one  of  these  proteins.  Noth- 
ing is  known  of  the  undetermined  residue  which  forms  from 
twenty-five  to  thirty-five  per  cent,  of  the  protein.  We  may 
expect  to  find  still  undiscovered  substances  among  the  protein 
decomposition  products." 


PERCENTAGE  COMPOSITION  OF  PROTEINS. 


Ammonia 

Glycocoll 

d-Alanin 

d-Valin 

1  -Leucin 

1  -Serin 

Cystin 

1  -Aspartic  acid. 
d-Glutamic  acid 

Lysin 

d-Arginin 

1  -Phenylalanin. 

Ty  rosin 

1-Prolin 

1  -Ox}'prolin 

1  -Tr\-ptophan.. 
1  -Histidin 

Total 


S5 


2.7 

20.0 
0.6 

2-3 

3-1 
7-7 


3-1 
2.1 
i.o 

-f- 


O 


3-5 
2.2 

+ 
18.7 

0.7 

2-5 

8.5 


3-8 

2-5 


Z  P 

5  s 


13 


0.9 
1.0 
10.5 
0.2 
0.06 
1.2 

II. o 

5-8 
4.8 
3-2 
4-5 
3-1 
0.2 

1-5 
2.6 


16.5 
0.8 
1.0 
2.1 
0.4 

o'6 
0.9 
2.7 
7.6 
0.4 
o 

5-2 

3-0 
o 

0.4 


5-II 

o 

2.00 

0.21 

5.61 

0.13 

0.45 
0.58 

37-33 
o 
3.16 

2-35 
1.20 
7.06 

+ 
0.61 


Id  K 


4.01 

0.89 
4-65 

0.24 

5-95 
0.74 
0.02 
0.91 
23.42 
1.92 
4.72 
1.97 
4-25 
4-23 

+ 
1.76 


42.6 


45-2 


35-3 


50.6 


41.6 


65.80 


59.68 


-|-  signifies  present. 
*  Abderhalden. 


t  Fischer,  Levene  and  Aders. 
t  T.  B.  Osborne. 


In  recent  years  the  idea  has  been  gaining  ground  that  pro- 
tein bodies  must  be  broken  up  into  amino-acids  before  absorp- 
tion in  the  intestine  (p.  186).  If  this  be  true  then  ingestion  of 
the  cleavage  products  of  protein  should  maintain  nitrogen 
equilibrium  in  the  same  way  as  the  ingestion  of  meat.  The 
first  experiments  in  this  direction  were  done  by  Loewi/  who  gave 
a  dog  pancreas  which  had  been  self-digested  until  all  the  protein 

'  Locwi:  "Archivfiirex.  Path,  und  Pharm.,"  1902,  Bd.  .xlviii,  p.  303. 


114  SCIENCE    OF   NUTRITION. 

had  been  converted  into  amino-acids,  as  was  indicated  by  the 
almost  complete  disappearance  of  the  biuret  reaction.  Fat  and 
carbohydrates  were  given  with  the  digest,  and  nitrogen  equilib- 
rium was  obtained  and  even  nitrogen  retention  accomplished. 
Thus,  in  one  experiment  covering  a  period  of  eleven  days,  pro- 
teolytic digestive  products  containing  an  average  of  6.08  grams 
of  nitrogen  were  given  daily,  of  which  only  5.19  grams  were 
eliminated  in  the  urine,  while  the  balance,  or  0.89  gram  of 
nitrogen,  was  retained  in  the  body  of  the  animal.  This  amount- 
ed to  9.79  grams  of  nitrogen  in  eleven  days.  Accompanying 
this  nitrogen  retention  was  one  of  0.649  gram  of  phosphoric  acid 
(P2O5),  an  amount  larger  than  was  necessary  for  the  upbuilding 
of  new  tissue  from  the  nitrogen  compounds  retained.  Loewi 
concluded  that  he  had  demonstrated  the  synthesis  of  new  protein 
within  the  organism. 

Lesser  ^  gave  a  pancreatic  digest  of  fibrin  to  a  dog  and  was 
unable  to  obtain  nitrogen  equilibrium. 

Henderson  and  Dean^  confirmed  Loewi  by  finding  that  they 
could  obtain  nitrogen  equilibrium  by  feeding  a  dog  with  the 
cleavage  products  of  meat  produced  by  treatment  with  sulphuric 
acid. 

Stiles  and  Lusk,^  on  the  contrary,  gave  a  fasting  diabetic  dog 
a  pancreatic  digest  of  meat  which  had  undergone  fourteen 
months  of  proteolytic  cleavage,  and  observed  that  the  nitrogen 
of  it  was  completely  eliminated  in  the  urine  without  protecting 
the  body  from  loss  of  protein,  which  protection  would  have  oc- 
curred had  meat  itself  been  administered. 

To  reconcile  these  differences  it  seemed  necessary  to  con- 
sider the  differences  in  methods  of  preparing  the  end  products 
of  the  protein  to  be  ingested.     Indeed,  Abderhalden  and  Rona* 

^Lesser:  " Zeitschrif t  fiir  Biologic,"  1904,  Bd.  xlv,  p.  506. 

^Henderson  and  Dean:  "American  Journal  of  Physiology,"  1903,  vol.  ix, 
p.  386. 

^  Stiles  and  Lusk:    "American  Journal  of  Physiology,"  1903,  vol.  ix,  p.  380. 

*  Abderhalden  and  Rona:  "Zeitschrift  fiir  physiologische  Chemie,"  1904, 
Bd.  xlii,  p.  528. 


THE  INFLUENCE  OF  PROTEIN  FOOD.  II5 

find  that  mice  live  on  casein  split  with  pancreatin  as  long  as  thev 
do  on  casein  alone;  whereas  they  die  much  earlier  if  the  casein 
has  been  submitted  to  peptic  and  then  pancreatic  digestion,  or 
if  it  has  been  broken  up  by  acid  hydrolysis.  Henriques  and 
Hansen  ^  also  find  that  casein  broken  up  by  acid  will  not  main- 
tain nitrogen  equilibrium  in  rats,  but  that  if  the  pancreas  of  the 
ox  and  a  small  piece  of  the  intestine  of  the  dog  (to  furnish  erepsin) 
be  digested  for  two  months  at  40°,  and  the  resulting  material 
given  to  rats,  nitrogen  equilibrium  will  be  maintained.  The 
authors  further  find  that  the  monoamino-acid  fraction  (the 
filtrate  after  precipitation  with  phospho  wolf  ramie  acid),  and 
also  the  alcoholic  extract  of  the  last-named  digest,  maintain 
rats  in  nitrogen  equilibrium.  The  residue  left  after  alcoholic 
extraction  will  not  do  so. 

Abderhalden  and  Rona^  have  accomplished  a  most  interest- 
ing experiment  upon  a  dog.  The  animal  was  given  daily  a 
constant  quantity  of  non-nitrogenous  foods  which  were:  fat, 
25  grams;  starch,  50  grams;  cane  sugar,  10  grams;  dextrose, 
5  grams.  The  dog  was  brought  into  nitrogen  equilibrium  by 
giving  meat  containing  2  grams  of  nitrogen.  Then  for  this 
were  substituted  the  amino  cleavage  products  of  casein,  pro- 
duced by  pancreatic  digestion  and  also  containing  2  grams  of 
nitrogen.  During  sixteen  days  on  this  diet  there  was  an  average 
daily  gain  of  0.12  gram  of  nitrogen  by  the  dog.  Then  casein 
hydrolized  by  acid  and  containing  2  grams  of  nitrogen  was 
administered  for  ten  days,  during  which  time  the  dog  lost  0.48 
gram  of  nitrogen  daily.  Amino-products  prepared  after  this 
fashion  will  therefore  not  preserve  nitrogen  equilibrium.  Lastly, 
the  diet  was  continued  without  any  nitrogenous  food.  The 
daily  waste  of  body  nitrogen  was  then  0.53  gram.  The  loss 
was  the  same  as  when  the  casein  hydrolized  by  acid  was  in- 
gested, indicating  that  this  particular  array  of  cleavage  prod- 
ucts had  no  protecting  power  over  the  body  protein. 

'Henriques  and  Hansen:  Ibid.,  1905,  Bd.  xliii,  p.  417. 
'  Alxlerhaldcn  and  Rona:   Ibid.,  1905,  Bd.  xliv,  p.  198. 


Il6  SCIENCE    OF   NUTRITION. 

The  absence  of  virtue  in  the  casein  hydrolized  by  acids  is 
attributed  by  Abderhalden  and  Rona^to  the  complete  destruc- 
tion of  all  polypeptids  (p.  59),  which  they  consider  to  be  the 
constructive  nuclei  (Bausteine)  of  protein.  When  the  latter  are 
present  a  partial  reconstruction  of  amino-acids  into  the  pro- 
teins of  blood  serum  is  possible. 

Henriques^  has  hydrolized  protein  by  digesting  it  with  trypsin 
and  erepsin  and  then  treating  with  20  per  cent,  sulphuric  acid 
on  the  water  bath.  The  resulting  material  consists  entirely  of 
amino-acids  with  no  admixture  of  polypeptids,  and  if  it  still 
gives  a  pronounced  tryptophan  reaction  it  will  support  the  or- 
ganism in  nitrogen  equilibrium.  In  the  absence  of  the  single 
amino-acid  tryptophan,  nitrogen  equilibrium  cannot  be  attained. 

It  seems  therefore  proved  that  amino-bodies  resulting  from 
certain  proteolytic  cleavages  may  be  the  equivalent  in  metabo- 
lism of  ingested  protein  itself. 

In  practical  dietetics  these  substances  can  have  no  value, 
as  they  tend  to  produce  diarrhea,  as  do  also  albumoses  and 
peptones  when  given  in  any  considerable  quantity.^  As  illus- 
trating this,  Cronheim*  finds  that  though  "Somatose"  is  more 
digestible  than  meat,  still  over  30  grams  is  undesirable  in  the 
daily  diet  of  a  man. 

It  is  certain  that  if  there  be  a  new  construction  of  protein 
in  the  body  from  the  amino-acids  formed  in  digestion  such 
new  proteins  are  characteristic  of  the  organism,  and  do  not 
possess  the  properties  of  the  proteins  originally  ingested.  To  il- 
lustrate this  Abderhalden  and  Samuely"  gave  to  a  horse  1500 
grams  of  gliadin,  a  vegetable  protein  which  contains  36.5  per 
cent,  of  glutamic  acid.     They  wondered  if    the  ingestion  of 

'Abderhalden  and  Rona:  "Zeitschrift  fiir  physiol.  Chemie,"  1906,  Bd. 
xlvii,  p.  397. 

^Henriques:    "Zeitschrift  fiir  physiologische  Chemie,"  1907,  Bd.  liv,  p.  406. 

^Voit:   "Miinchener  med.  Wochenschrift,"  1899,  Nos.  6  and  7. 

*  Cronheim:  "Pfliiger's  Archiv,"  1904,  Bd.  cvi,  p.  17. 

^Abderhalden  and  Samuely:  "Zeitschrift  fiir  physiologische  Chemie," 
1905,  Bd.  xlvi,  p.  193. 


THE  INFLUENCE  OF  PROTEIN  FOOD.  I17 

such  a  protein  would  in  any  way  modify  the  composition  of  the 
proteins  of  the  blood  serum,  of  serum  globulin  which  under  or- 
dinary circumstances  contains  8.5  per  cent.,  and  of  serum 
albumin  which  contains  7.7  per  cent,  of  glutamic  acid.  Their 
results  were  as  follows: 

INFLUENCE  OF  GLIADIN  INGESTION  ON   THE   PER   CENT    OF 
GLUTAMIC  ACID  IN  THE  SERUM  PROTEINS  OF  THE  HORSE. 

After  Ingesting 
Normal    After  Fasting      ^5°°  G.  Gliadin. 
Experiment.  Day.        7  or  8  Days.       Day  i.  Day  2. 

1 8.85  8.20  7.88  8.25 

II 9.52  8.52  8.00 

It  is  evident  that  gliadin  which  contains  so  large  a  propor- 
tion of  glutamic  acid  is  without  influence  on  the  composition  of  the 
blood  serum.  The  larger  part  of  the  glutamic  acid  is  probably 
deaminized  in  the  intestinal  wall  before  reaching  the  blood. 
Abderhalden  conceives  that  such  proportions  of  the  amino- 
acids  within  the  gliadin  complex  as  are  available  for  the  forma- 
tion of  new  serum  albumin  and  serum  globulin  are  used  for  the 
generation  of  these  proteins. 

It  has  already  been  stated  (p.  58)  that  if  the  serum  of  a  dog 
be  injected  into  the  blood-vessels  of  another  dog  the  nitrogen 
of  it  will  be  eliminated  in  the  urine.  This  is  also  true  of  pro- 
teins foreign  to  the  organism,  and  these  likewise  act  in  a  toxic 
manner  to  destroy  body  protein.  Thus  Mendel  and  Rock- 
wood^  have  shown  that  if  edestin,  a  pure  crystalline  protein 
prepared  from  hemp  seed,  be  injected  intravenously  into  a 
fasting  dog,  there  is  for  two  days  a  metabolism  of  protein  which 
is  much  greater  than  that  of  former  days  plus  that  of  the  edestin 
administered.  The  same  truth  holds  when  casein  is  injected. 
Similar  injection  of  horses'  serum  into  dogs  appears  to  have  no 
toxic  action  (Rona  and  Michaelis'').  This  work  is  of  interest 
in  connection  with  the  subject  of  anaphylaxis,  called  also  the 

'Mendel  and  Rockwood:  "American  Journal  of  Phy.siology,"  1904.  vol.  xii, 
P-  35°- 

'Rona  and  Michaelis:  "  Pfliiger's  Archiv,"  1908,  cxxi,  p.  163;  and  1908, 
cxxiii,  p.  40O. 


Il8  SCIENCE    OF   NUTRITION. 

Theobald  Smith  phenomenon,  which  has  been  especially  inves- 
tigated by  Rosenau  and  Anderson.  Injections  of  a  protein 
foreign  to  the  organism  render  the  body  sensitive  to  a  second 
injection  of  the  same  protein.  Large  or  small  amounts  of  for- 
eign protein  may  be  injected  in  the  first  instance  v\^ithout  intoxi- 
cation, but  if  the  animal  be  once  "sensitized"  a  small  amount 
of  the  same  protein  will  terminate  the  animal's  existence. 
It  has  recently  been  stated  by  Wells  ^  that  the  injection  of 
so  minimal  an  amount  as  one  millionth  of  a  gram  of  pure  crys- 
talline egg  albumin  will  "sensitize"  a  guinea  pig  so  that  a  sub- 
sequent injection  into  the  blood  of  a  tenth  of  a  milligram  of  the 
same  substance  is  lethal,  although  such  a  dose  given  in  the  first 
instance  would  not  have  injured  the  animal.  It  is  evident, 
therefore,  that  the  alimentary  canal  cannot  allow  the  passage 
of  proteins  without  changing  them.  This  also  explains  the 
complete  immunity  of  the  organism  to  snake  venom  which  has 
been  swallowed. 

The  effect  of  copious  drinking  of  water  upon  protein  metab- 
olism has  been  made  the  subject  of  various  studies.  A  small 
increase  in  nitrogen  elimination  has  usually  been  noted.  This 
was  first  established  by  Voit,  who  explained  it  as  due  to  an 
increased  circulation  which  influenced  the  flow  of  the  intra- 
cellular fluids.  Heilner^  has  recently  shown  that  giving  2000 
c.c.  of  water  to  a  fasting  dog  on  two  successive  days  raises  his 
urinary  nitrogen  from  3.15  grams  to  4.09  and  3.58  grams  on 
the  two  days  of  water  ingestion,  and  then  the  nitrogen  excretion 
falls  to  2.22  and  2.62  on  the  following  days.  In  this  experi- 
ment the  carbon  dioxid  excretion  was  very  slightly  increased 
and  the  temperature  of  the  dog  was  not  affected.  The  quantity 
of  urine  rose  from  90  c.c  to  2050  c.c. 

Straub^  found  that  an  extra  insiestion  of  2000  c.  c.  of  water 


^  Wells:  Proceedings  of  the  Society  for  Experimental  Biology  and  Medicine, 
8,  vi,  p.  I. 

^Heilner:   "Zeitschrift  fiir  Biologie,"  1906,  Bd.  xlvii,  p.  541. 
^  Straub:  Ibid.,  1899,  Bd.  xxxvii,  p.  527. 


THE  INFLUENCE  OF  PROTEIN  FOOD.  IIQ 

in  a  man  who  was  in  nitrogen  equilibrium  on  a  diet  containing 
20.56  grams  of  nitrogen  had  no  effect  on  protein  metabolism; 
whereas  Hawk/  who  gave  less  protein  nitrogen  but  more  water, 
found  that  the  ingestion  of  4500  c.c.  of  water  caused  the  urinary- 
nitrogen  to  rise  from  11.03  to  12.48  on  the  first  day,  and  11.82 
on  the  second  day,  with  a  fall  to  10.91  grams  on  the  succeeding 
day  when  no  water  was  given.  Hawk  interprets  the  action  of 
copious  water-drinking  as  twofold, — first,  to  cause  a  removal 
of  any  accumulation  of  nitrogenous  decomposition  products 
from  the  organism,  as  was  indicated  by  the  greater  increase  of 
12.8  per  cent,  in  the  nitrogen  elimination  of  the  first  day;  and, 
second,  to  cause  a  true  increase  in  protein  metabolism,  as  was 
indicated  by  the  smaller  increase  of  6.8  per  cent,  on  the  second 
day  of  water  ingestion. 

Abderhalden  and  Bloch^  have  given  a  fixed  diet  to  a  person 
suffering  from  alkaptonuria  (see  p.  136)  and  on  one  of  the  days 
of  the  experiment  have  caused  him  to  ingest  5  liters  of  water. 
The  results  of  their  analyses  gave  the  following  figures : 

N  IN         HOMOGENTISIC 

N  Balance.  Urine.  Acid. 

Normal  Food +  1.36  18.2  10.52 

"       +  5  L.  Water —2.19  21.75  10.18 

"  "      +  1.47  18.09  10.27 

Abderhalden  believes  that  the  constancy  of  the  output  of 
homogentisic  acid  indicates  a  constancy  of  protein  metabolism 
throughout,  whereas  the  rise  in  total  nitrogen  elimination  in  the 
urine  represents  a  washing  out  of  the  nitrogenous  end-products 
as  a  result  of  the  large  ingestion  of  water. 

One  of  the  striking  characteristics  of  starvation  metabolism 
was  shown  to  be  its  extreme  regularity  from  hour  to  hour  and 
from  day  to  day.  What,  then,  is  the  hour-to-hour  metabolism 
after  meat  ingestion  ? 

'Hawk:   "University  of  Pennsylvania  Medical  Bulletin,"  March,  1905. 
^Abderhalden  and  Bloch:    "2^itschrift  fiir  physiologische  Chera.,"  1907, 
Bd.  5.3,  p.  464. 


I20 


SCIENCE    OF   NUTRITION. 


The  classical  experiments  of  Voit^  and  of  Feder^  have  been 
more  fully  worked  over  by  G  ruber.  Gruber^  fed  a  dog  with 
500,  1000,  and  1500  grams  of  meat  on  different  days.  He 
collected  the  urine  every  two  hours  after  the  meal  and  determined 
the  nitrogen  output.  The  curves  of  nitrogen  elimination  under 
these  circumstances  are  as  follows  : 

fij in.  jgrams  /?er  Zhrs. 


8 

1 

/ 

/\ 

\, 

6 

/ 

/ 

V 

N, 

\ 

S 

/ 

\ 

/ 

r 

\ 

4 

/ 

V, 

^, 

\ 

/ 

/ 

\ 

\ 

3 

>'l 

/^ 

^, 

\ 

\ 

\ 

/ 

\ 

\ 

\ 

•> 

xl 

/ 

\ 

\ 

\ 

J 

\ 

N, 

\ 

\, 

\ 

7 

\ 

\ 

V 

N, 

\ 

v.. 

— • 

^"^ 

< 

3    k 

'      J. 

i- 

$  t 

; 

0    1 

z    1 

^   1 

6    1 

?      -2 

0    2 

Z     2 

Hours 

Fig.  5. — I,  after  500  g.  meat  +  50  g.  fat  +  350  c.c  water;  2,  after  1000  g. 
meat  +  200  c.c.  water:  3,  after  1500  g.  meat  +  500  c.c.  water.  On  each  of  these 
daySj.the  animal  was  in  nitrogen  equihbrium. 

It  is  evident  that  there  is  an  early  elimination  of  protein 
nitrogen  which  here  reaches  a  maximum  between  five  and  seven 


^Voit:   "Physiologische  Untersuchungen,"  Augsburg,  1857,  p.  42. 
^Feder:   "Zeitschrift  fiir  Biologic,"  1881,  Bd.  xvii,  p.  541. 
^Gruber:  Ibid.,  1902,  Bd.  xlii,  p.  421. 


THE    INFLUENCE    OF    PROTEIN    FOOD.  121 

hours  after  feeding,  and  that  the  hour  of  the  maximum  excre- 
tion is  delayed  by  increasing  the  quantity  of  meat  ingested. 

It  is  apparent,  therefore,  that  the  protein  metabohsm  as  il- 
lustrated by  the  curve  of  nitrogen  elimination  is  quite  different 
from  the  even  metabolism  of  starvation. 

Haas^  in  experiments  on  man  finds  that  the  curve  of  nitrogen 
elimination  after  a  breakfast  consisting  of  milk,  bread,  butter, 
and  cheese  always  shows  two  maxima,  the  first  in  the  second 
hour  and  the  second  in  the  fifth.  The  first  rise  in  the  curve  is 
due  to  the  removal  of  nitrogenous  end-products  already  in  the 
system  and  is  caused  by  the  early  absorption  of  liquids  taken 
with  the  food.  The  second  rise  corresponds  to  the  absorption 
of  food-protein.  Haas  believes  this  to  be  the  true  explanation, 
because  if  diuresis  be  first  induced  by  drinking  tea,  with  a  con- 
sequent washing  out  of  urea  from  the  body,  then  partaking  of 
breakfast  no  longer  causes  so  high  a  primary  rise  of  nitrogen 
elimination,  nor  is  the  total  elimination  so  great  as  in  the  experi- 
ments without  preliminary  diuresis.  The  experiment  shows 
that  for  short  periods  the  nitrogen  excretion  is  not  a  true  index 
of  urea  production.  Severe  muscular  work  has  no  influence 
upon  the  character  of  the  curve  described  except  when  the  quan- 
tity of  urine  produced  is  diminished,  in  which  case  the  urea 
elimination  is  also  reduced. 

If  protein  is  given  to  a  fasting  dog  the  rapidity  of  its  destruc- 
tion is  greater  the  longer  the  animal  has  been  fasting.^ 

If  protein  or  amino-acids  such  as  glycocolF  and  aspartic 
acid  are  administered  the  resulting  nitrogen  increase  in  the  urine 
is  entirely  due  to  urea.* 

If  in  man  various  proteins  be  added  to  an  already  sufficient 
mixed  diet  (superposition  experiments),  the  rate  of  destruction 

'Haas:     "Biochemischc   Zcilschrifl,"    1908,    Bd.   xii,   p.    203. 

'  Falta  and  Gig(m:    "  Biochemische  Zeilschrift,"  1908,  vol.  xiii,  p.  269. 

'  Brugsch  and  Hirsch:  "Zeitschrift  fiir  cxpcrimcntclle  Pathologic  und 
Therapie,"  1906,  Bd.  iii,  ]>.  638. 

*  Levene  and  Kobcr:  "American  Journal  of  Physiology,"  1909,  vol.  xxiii, 
p.  324. 


122 


SCIENCE    OF   NUTRITION. 


of  the  added  protein  as  indicated  by  the  extra  N  eliminated  in 
the  urine  varies  with  the  character  of  the  protein.  Such  ex- 
periments were  first  devised  by  Faha/  who  estabhshed  the  fol- 
lowing classification  of  proteins  in  the  order  of  the  rapidity  of 
their  destruction:  a.  gelatin,  casein,  serum  albumin,  fibrin; 
h.  blood  globulin;  c.  hemoglobin;  d.  egg  albumin.  Hama- 
lainen  and  Helme^  continued  these  experiments  and  they  also 
investigated  the  elimination  of  sulphur  and  phosphorus.  They 
gave  a  man  weighing  66  kilograms  a  diet  containing  3650  cal- 
ories and  5  grams  of  nitrogen.  On  this  diet  they  superimposed 
on  different  days  the  following  amounts  of  proteins : 

800  g.  white  of  egg  =  14.40  g.  N  -|-  1.56    g.  S 

57  g.  proton  =    6.94  g.  N  -I-  0.419  g.  S 

320  g.  veal  =  13.44  g.  N  +  0.832  g.  S 

and  noticed  the  time  of  the  elimination  of  nitrogen,  sulphur,  and 
phosphorus  through  the  kidney.  It  was  six  days  before  all  the 
nitrogen  of  the  ingested  white  of  egg  was  eliminated,  whereas 
that  in  veal  and  proton  required  only  two  or  three  days.  This 
is  evident  from  the  following  table: 

DAILY  PERCENTAGE  ELIMINATION  OF  THE  NITROGEN,  SUL- 
PHUR, AND  PHOSPHORUS  OF  INGESTED  PROTEIN  SUPER- 
IMPOSED ON  AN  ADEQUATE  DIET. 


Egg-white. 

Proton. 

Veal. 

Day. 

N. 

s. 

N. 

S. 

N. 

S. 

P. 

I 

21 
21 
22 
II 

14 
II 

41.4 

32.2 

14.4 

4-3 

5-5 

2.4 

64 
10 

13 
13 

90 
10 

56 
26 
18 

74.2 

17.8 

8.0 

"" 

60 

2 

24 
16 

2 

A 

C 

6 

"" 

The   rapidity   of   the   sulphur   elimination   is   everywhere 
noticeable.    The  "nitrogen  lag"  in  the  case  of  white  of  egg  is 

^  Falta:  "Deutsches  Archiv  fur  klinische  Medizin,"  Bd.  xxxvi,  1906,  p.  517. 
^  Hamalainen  and  Helme:    "Skan.  Archiv  fiir  Physiologie,"  1907,  Bd.  xix, 
p.  182. 


THE  INFLUENCE  OF  PROTEIN  FOOD. 


123 


pronounced  and  may  be  due  to  the  retention  of  peptids  which 
are  only  slowly  metabolized  or  it  may  be  due  to  the  retention 
of  amino-acids  themselves. 

That  glycocoU  as  such  is  normally  present  within  the  organ- 
ism has  already  been  mentioned  in  connection  with  the  fact  that 
when  benzoic  acid  is  ingested  there  is  at  first  a  considerable 
output  of  hippuric  acid,  and  this  is  followed  by  a  constant 
output  of  the  substance  in  proportion  to  the  protein  metabolized. 
Furthermore  Murlin^  has  shown  that  if  glycocoll  be  ingested 
with  carbohydrates,  then  instead  of  being  converted  into  urea 
it  is  quite  largely  retained,  so  that  nitrogen  equilibrium  is  almost 
obtained  on  the  first  day  of  ingestion.  On  continuing  the  same 
diet,  however,  the  capacity  to  retain  the  glycocoll  diminishes,  as 
is  witnessed  by  the  increasing  elimination  of  nitrogen  in  the 
urine. 


RETENTION     OF     GLYCOCOLL    INGESTED     WITH     CARBOHY- 
DRATES. 


Day. 

Cal. 
PER  Kg. 

NiN 

Urine. 

N 
Balance. 

I 

5th  day  fasting. 
7  S-  glycocoll  — 

1.332  N 

142 
142 
142 
140 
140 

1.288 

1-457 
1. 612 
2.006 
0.987 
0.713 

—1.288 

2 

— 0.125 

■2 

—0.280 

— 0.674 

C 

—0.987 

6 

— 0.713 

This  experiment  should  be  interpreted  in  the  light  of  the 
fact  that  the  carbohydrates  ingested  would  of  themselves  re- 
duce the  fasting  protein  metabolism  to  one-third  its  original 
amount  (i.  e.,  from  1.28  to  0.43  grams  N;  see  p.  173).  Since 
after  removing  glycocoll  from  the  ingesta  and  continuing  the 
liberal  administration  of  carbohydrate  the  urinary  nitrogen  did 
not  fall  to  one-third  the  fasting  amount,  Murlin  concluded  that 
this  was  due  to  a  gradual  elimination  of  the  glycocoll  nitrogen 
previously  ingested. 

'Murlin:    "American  Journal  of  Physiology,"   1907,  vol.  xx,  p.   250. 


124 


SCIENCE    OF   NUTRITION. 


This  experiment  indicates  why  in  the  presence  of  carbohy- 
drates protein  nitrogen  may  be  only  slowly  eliminated,  and  gives 
an  elementary  example  of  "nitrogen  lag." 

Liithje^  has  noted  a  similar  nitrogen  retention  after  giving 
glycocoll  and  asparagin  and  has  speculated  on  the  formation 
of  an  "amino-sugar." 

Dr.  C.  G.  L.  Wolf  has  kindly  placed  some  unpublished  work 
at  the  writer's  disposal.  Wolf  gave  a  man  a  constant  and  suffi- 
cient diet  containing  7  grams  of  nitrogen,  of  which  1.2  grams  were 
given  at  breakfast  and  the  rest  at  an  evening  meal.  Upon  the 
"normal"  breakfast  he  "superimposed"  different  materials. 
The  gross  results  of  the  experiments  during  twenty-four-hour 
periods  were  as  follows: 


Food  Superimposed. 

Balance  to  Body. 

Grams. 

Content  of: 

N. 

Kind. 

N. 

s. 

S. 

None  (normal  period) 

Veal  cutlets 

500 
25 
50 
10 

17.I 

11.66 
7.86 
1. 14 

1.02 
2.65 

— 2.0 

+    8.7 
-F*i.8 
-|-*4-o 
— c-5 

—0.15 
+  0.23 

Urea 

Alanin 

Cvstin 

+  0.73 

*  Feces  not  analyzed. 

The  more  detailed  procedure  included  the  analysis  of  the 
urine  every  hour  for  sixteen  hours  after  ingestion  of  the  break- 
fast, and  some  of  the  results  are  presented  in  the  curve  furnished 
by  Dr.  Wolf  and  shown  in  Fig.  6.  The  curve  of  total  nitrogen 
elimination  is  here  given  and  in  every  case  this  total  nitrogen 
elimination  consisted  almost  entirely  of  urea  nitrogen. 

After  ingestion  of  the  very  soluble  urea  it  is  noticed  that  there 
is  a  rapid  rise  in  the  nitrogen  elimination  in  the  urine.  The 
same  is  true  after  the  ingestion  of  alanin,  the  nitrogen  of  which  is 
rapidly  converted  into  urea.     The  nitrogen  of  the  veal  cutlets, 

^Liithje:   "Congress  fiir  innere  Medizin,"  1906,  p.  44. 


Grams  1 


11      13     15 


Breakfast  Diets 
(with  total  N  content) . 

(a)  Normal  1.20  N. 

(b)  Urea  12.86  N.     C.3 
(c)  Cystin  2.37  X. 

(d)  Veal  cutlets  18.32  N. 

(e)  Alanin  9.00  N. 


(b,  d) 


(c) 


(a) 
(e) 


(c) 


i^        (d1 


(e) 


(With  total  S  content). 

(c)  Cystin  2.75  S.  "-"^ 
(a)  Normal  o.io  S. 

(d)  Veal  cutlets  1.13  S 


1       3       5      7       9       11     13     15  Hours. 

Fig.  6.— The  diiTcrent  curves  begin  at  the  level  of  the  excretion  of  urinary 
N  or  S  determined  during  an  early  hour  previous  to  breakfast.  The  arrow 
represents  the  time  an  hour  after  food  ingestion,  and  shows  no  increased  excre- 
tion, except  in  the  cases  of  the  very  soluble  urea  and  alanin.  The  secondary 
rises  in  the  curves  in  the  tenth  to  twelfth  hours  are  due  to  the  ingestion  of  supper. 

Upper  Par/.— Represents  the  hourly  e.\(  retion  of  total  N  after  ingesting 
(a)  "normal"  breakfast  containing  1.20  g.  N;  (b)  same  breakfast  plus  urea 
with  11.66  g.  N;  (c)  same  breakfast  plus  cystin  with  1.14  g.  N;  (d)  same 
breakfast  jjIus  veal  cutlets  with  17.1  g.  N;  (e)  same  breakfast  plus  alanin 
with  7.86  g.  N.  •  ,       /  X 

Lower  Part. — Represents  excretion  of  S  during  the  same  intervals:  (a) 
"normal"  breakfast  containing  o.i  g.  S;  (c)  same  breakfast  plus  cystin  with 
2.65  g.  S;   (fl)  same  Vjreakfasl  plus  veal  cutlets  with  1.02  g.  S. 

125 


126 


SCIENCE    OF    NUTRITION. 


however,  requires  a  much  longer  time  for  its  eHmination.  The 
sulphur  from  cystin  is  for  the  most  part  oxidized  to  sulphate 
and  is  gradually  excreted.  After  the  ingestion  of  veal  cutlets 
the  sulphur  and  nitrogen  curves  run  parallel  to  each  other. 
If  we  turn  from  the  nitrogen  elimination  to  that  of  the  car- 
bon in  the  respiration,  it  will  be  found  that  here  the  elimina- 
tion is  comparatively  even.  Frank  and  Trommsdorf  ^  gave  a 
dog  1191  grams  of  meat  which  had  been  freed  from  extractives 
by  means  of  lukewarm  water.  The  nitrogen  and  carbon  of  the 
urine  and  feces  and  the  carbon  of  the  respiration  were  deter- 
mined, and  from  these  data  the  protein  and  fat  metabolism  were 
calculated  in  the  usual  manner.  From  this  the  heat  produced 
was  estimated.     The  essential  results  were  thus  tabulated: 

VARIATION  IN  METABOLISM  AFTER  MEAT  INGESTION. 


No.  OF  Hours. 

Per  Hour. 

Period. 

N  in  Urine. 

C  in  Res- 
piration. 

Calories 
from  Meta- 
bolism. 

24 

4  h.    9  m. 
3  h.  14  m. 

5  h.  44  m. 
ID  h.  53  m. 

(night) 

0.1944 

0.917 

1-373 
1.592 
1.064 

2.968 

3.862 
3.886 
3.872 
3-493 

36.72 

43-94 
41-53 
41.00 
38.46 

Meat  Ingested: 

First  period  after  meat 

Second  "         "           "    

Third     "         "           "    .... 
Fourth  "         "           " 

It  is  evident  that  while  the  curve  of  the  nitrogen  elimination 
shows  a  maximum  rise  to  nearly  eight  times  that  of  fasting  and 
varies  greatly,  the  carbon  curve  is  much  more  even  and  is  not 
much  above  that  found  in  starvation.  The  maximum  rise  in 
heat  production  occurs  in  the  first  four  hours  after  the  inges- 
tion of  meat  and  amounts  to  twenty  per  cent.  The  heat  pro- 
duction falls  during  the  night  hours. 

Rubner^  has  obtained  similar  results  after  giving  460  grams 

^  Frank  and  Trommsdorf :   "Zeitschrift  fiir  Biologic,"  1902,  Bd.  xliii,  p.  266. 
^Rubner:   "Gesetze  des  Energieverbrauchs,"  1902,  p.  365. 


THE  INFLUENCE  OF  PROTEIN  FOOD. 


127 


of  washed  meat  to  a  dog  weighing  24  kilograms.     His  calcula- 
tions show  the  following  metabolism  during  six-hour  periods: 

VARIATION  IN  METABOLISM  AFTER  MEAT  INGESTION. 
1 — 

First  Day  of  Ingestion. 


Time  of  Day. 


Day,     9-3 

3-9 
Night,  9-3 

Total... 


N  in  Urine. 


5.06 
6.II 
4.64 
2-76 

18.6 


Cal.  from 
Protein. 


I35-I 

163.0 

123.8 

73-6 
495-5 


Cal.  from 
Fat. 


143-9 

85.2 

105.4 

169.5 

504.0 


Calories 
Total. 


279.0 
248.2 
229.2 
243.1 

999-5 


Third  Day  of  Ingestion. 


Time  of  Day. 


Day,     9-3 

3-9 
Night,  9-3 

3-9 
Total  .. 


N  in  Urine. 


5-57 
8.94 
5-32 
2.66 

22.5 


Cal.  from 
Protein. 


148.7 

238.7 

142.0 

71.0 

600.4 


Cal.  from 
Fat. 


130.4 
33-4 
76.3 

162.4 

402.5 


Calories 
Total. 


279.1 
272.1 
218.3 

233-4 

1002.9 


The  nitrogen  curve  varies.  The  total  heat  production  is 
greatest  during  the  hours  immediately  following  the  ingestion 
of  protein,  but  is  otherwise  comparatively  even. 

If  we  pass  from  the  consideration  of  protein  metabolism,  as 
indicated  by  the  nitrogen  curve,  to  the  consideration  of  the 
intermediary  metabolism  of  protein  we  can  see  more  clearly  that 
the  curve  of  protein  nitrogen  excretion  is  not  a  true  index  to 
the  sum  of  the  activities  contributed  to  the  cells  by  protein 
metabolism. 


CHAPTER  V. 

THE  INFLUENCE  OF  PROTEIN  FOOD. 

PART  TWO. 

The  term  "intermediary  metabolism"  with  which  so  much 
modern  work  is  intimately  associated  was  used  by  Bidder  and 
Schmidt  on  the  first  page  of  their  celebrated  "  Verdauungssaf te 
und  Stoffwechsel, "  published  in  1852. 

Voit^  believed  that  there  was  an  early  clea.vage  of  the  pro- 
tein molecule  into  a  nitrogenous  portion  and  a  non-nitrogenous 
portion,  a  cleavage  involving  the  liberation  of  only  a  small 
amount  of  energy;  that  there  was  a  rapid  combustion  of  the 
nitrogenous  radicle,  as  shown  by  the  elimination  of  the  nitro- 
genous end-products  in  the  urine;  and  that  the  non-nitrogenous 
radicle  which  contained  the  major  part  of  the  potential  energy 
of  the  protein  molecule  might  in  part  be  temporarily  stored 
either  as  glycogen  or  fat  and  be  gradually  doled  out  to  the 
tissues  as  the  need  required. 

Claude  Bernard  believed  that  glycogen  could  arise  from 
protein.  Wolffberg^  let  fowls  fast  two  days  to  remove  the  gly- 
cogen and  then  for  two  days  gave  meat  powder  which  was 
free  from  carbohydrate.  Two  fowls,  killed  during  the  inter- 
val of  protein  digestion,  showed  considerable  glycogen  in 
their  livers  (1.56  and  1.45  per  cent.)  and  muscles  (0.251  and 
0.454  per  cent.),  much  more  than  would  have  been  present  in 
starvation.  Two  similar  fowls,  killed  seventeen  and  twenty- 
four  hours  after  the  last  protein  ingestion,  contained  much  less 

1  Voit:   "Zeitschrift  fiir  Biologic,"  1891,  Bd.  xxviii,  p.  291. 
^Wolffberg:  Ibid.,  1876,  Bd.  xii,  p.  278. 
128 


THE  INFLUENCE  OF  PROTEIN  FOOD. 


129 


glycogen  in  their  livers  (0.145  and  0.22  per  cent.)  and  muscles 
(0.2 1 1  and  0.162  per  cent.).  This  origin  of  glycogen  from  pro- 
tein was  fully  confirmed  by  Kiilz  ^  in  a  very  extended  series  of 
experiments  in  which  chopped  meat,  fully  extracted  with  warm 
water,  was  made  the  basis  of  the  ingesta.  It  became  evident 
from  these  experiments  that  if  sufficient  protein  were  given  to  an 
animal,  part  of  the  protein  carbon  could  be  retained  as  glycogen. 
It  has  long  been  believed  that  sugar  arises  from  protein  in 
diabetes.  Kossel  ^  first  suggested  that  hexone  bases,  leucin,  and 
other  protein  end-products,  contained  six  atoms  of  carbon,  as 
did  also  the  ordinary  hexose  sugars,  such  as  dextrose,  levulose, 
and  galactose.  The  theory  of  the  origin  of  sugar  in  diabetes 
from  these  amino-products  was  strongly  advocated  by  Friedrich 
jSIiiller.^  The  definite  proof  of  this  was  afforded  by  Stiles  and 
Lusk,^  who  gave  a  mixture  of  amino-bodies  prepared  by  the  pan- 
creatic proteolysis  of  meat  to  a  dog  rendered  diabetic  with 
phlorhizin.  The  mixture  was  free  from  protein.  The  nitrogen 
ingested  was  entirely  eliminated  in  the  urine,  and  for  each 
gram  of  such  nitrogen  2.4  grams  of  extra  sugar  appeared  in  the 


urme. 


In  the  Chapter  on  Diabetes  it  will  be  shown  how  amino- 
acids  of  the  general  formula  CnHgnNHaCOOH  may  be  deamin- 
ized  with  the  formation  of  ammonia  (which  is  convertible  into 
urea  in  the  liver)  and  organic  oxyacids.  The  latter  are  either 
directly  available  for  oxidation  or  they  are  wholly  or  in  part 
convertible  into  dextrose,  in  which  form  they  can  be  used  by  the 
organism.  The  heat  value  of  protein  lies  in  this  deaminized 
or  denitrogenized  remainder.  (See  p.  163.)  The  earlier  state- 
ments of  Bidder  and  Schmidt  (see  p.  20)  and  of  Voit  (see  p. 
1 28)  have  therefore  been  fully  justified,  and  it  is  right  to  believe 
that  the  true  energy-yielding  materials  formed  in  the  deamina- 

'  Kiilz:   "Ludwig's  Festschrift,"  1890,  p.  83. 
'Kossel:    "Deutsche  medizinische  Wochenschrift,"  i8g8,  j).  58, 
'  Miillcrand  Seeman:  Ibid.,  1899,  p.  209. 

*  Stiles  and  Lusk:   "American  Journal  of  Physiology,"  1903,  vol.  ix,  p.  380. 
9 


I30 


SCIENCE    OF   NUTRITION. 


tion  of  protein  are  like  fat  or  carbohydrate  in  their  value  to 
the  organism. 

As  regards  the  liver,  even  after  severe  artificial  necrosis,^ 
or  the  wide-spread  action  upon  the  cytoplasm  of  the  parenchy- 
matous cells  which  follows  injection  of  hydrazin,^  the  urea- 
forming  function  still  remains  apparently  undamaged.  Jackson 
and  Pearce  point  out  that  this  is  one  of  the  many  "factors  of 
safety"  in  the  body  in  the  sense  of  Meltzer.''' 

Considerable  sugar  may  originate  from  protein  in  the  course 
of  its  ordinary  metabolism.  The  question  arises  at  what  time 
during  the  metabolism  does  this  sugar  become  available  for 
combustion  in  the  organism?  This  question  was  answered  by 
an  experiment  of  Reilly,  Nolan,  and  Lusk.*  These  authors  gave 
a  fasting  phlorhizinized  dog  500  grams  of  meat' and  collected 
the  urine  in  two  three-hour  and  one  six-hour  period.  The 
results  were  as  follows: 

EXCRETION    OF    DEXTROSE    AND     NITROGEN    BEFORE    AND 
AFTER  INGESTING  500   GRAMS    OF  MEAT  IN  DIABETES. 

Dextrose.     Nitrogen.         D  :  N. 

Preceding  3  hours 

First      3  hours  after  feeding 

Second  3       "       "  "        

Third    3       "       "  "        

Fourth  3       "       "  "        

Following  3  hours 


5-96 

1-75 

3-41 

12.43 

2.52 

4.92 

14.70 

3-76 

3-91 

11.23 

3-8S 

2.92 

11.23 

3-85 

2.92 

6.34 

1.78 

3-56 

The  normal  fasting  relation  between  dextrose  and  nitrogen 
changed  immediately  upon  the  ingestion  of  meat.  During  the 
first  hours  more  dextrose  was  eliminated  than  corresponded 
to  the  nitrogen  in  the  urine.  During  the  later  hours  this  pro- 
portion was  reversed.  The  sugar  elimination  therefore  took 
place  decidedly  before  that  of  the  nitrogen.     This  is  shown  in 

^Jackson  and  Pearce:  "Journal  of  Experimental  Medicine,"  1907,  vol. 
ix,  p.  552. 

^Underhill  and  Kleiner:  "Journal  of  Biological  Chemistry,"  1908,  vol. 
iv,  p.  165. 

^Meltzer:    "The  Harvey  Lectures,"  1906-07,  p.  139. 

^Reilly,  Nolan,  and  Lusk:  "American  Journal  of  Physiology,"  1898  vol  i 
P-  395- 


THE  INFLUENCE  OF  PROTEIN  FOOD. 


131 


the  following  calculation  of  the  percentage  elimination  of  nitro- 
gen and  dextrose  in  three-hour  periods  following  the  ingestion 
of  500  grams  of  meat  in  the  above  experiment: 


Dextrose. 

During  first       3  hours 25.06 

"      second  3     "      29.64 

"      third     3     "      22.65 

"      fourth  3     "      22.65 


Nitrogen. 
18.02 
26.90 

27-54 
27-54 


100.00 


The  relations  are  represented  in  the  following  curve; 


Grama  Jv.forShnS 

4 


J 

j       / 

^•''^ 

\  \ 

/ 

i  / 

\  \ 

\\ 

// 

\\ 

drains  U.  for  Shrs 
10-6 

71 
3S 


Ho  urs . 


iZ 


Fig.  7. 


Nitrogen. 

Dextrose. 

-Curve  showing  the  elimination  of  dextrose  before  nitrogen  after  meat 
ingestion  (500  grams)  in  diabetes. 


That  the  dextrose  production  from  the  meat  ingested  was 
proportional  to  the  protein  destroyed  is  evident  from  the  follow- 
ing comparison,  in  which  the  sum  of  the  dextrose  and  nitrogen 
eliminated  in  the  twelve  hours  is  considered.  Nitrogen  and 
dextrose  double  in  quantity  after  the  ingestion  of  meat,  but 
their  ratio  remains  the  same  as  in  starvation. 

Dextrose.  Nitrogen.  D:N. 

Fasting  12  hours 23.87               7.00  3.41 

After  500  g.  meat,  12  hours 49-59             14.00  3.54 

Subsequent  12  hours 25.36               7. 11  3.56 


132 


SCIENCE    OF   NUTRITION. 


The  curve  shows  that  there  is  an  early  production  of  sugar 
from  protein  which  may  be  liberated  in  metabolism  before  the 
nitrogen  belonging  to  the  protein  is  eliminated  in  the  urine.  A 
similar  early  production  of  sugar  from  protein  has  also  been 
observed  after  feeding  dogs  with  meat  in  pancreas  diabetes.^ 

Since  one  gram  of  nitrogen  in  the  urine  represents  a  destruc- 
tion of  6.25  grams  of  meat  protein,  and  since  there  is  simultane- 
ously an  average  elimination  of  3.65  grams  of  dextrose  in  phlor- 
hizin  diabetes,  it  may  be  calculated  that  the  sugar  production 
from  meat  amounts  to  58  per  cent,  by  weight  of  the  meat  pro- 
tein metabolized  and  may  contain  52.5  per  cent,  of  its  total' 
available  energy  (p.  70). 

Another  calculation  shows  that  of  the  carbon  from  protein 
which  is  ordinarily  eliminated  in  the  respiration  63.2  per  cent, 
passes  through  the  dextrose  stage  (see  p.  288). 

After  the  ingestion  of  protein  in  the  normal  organism  this 
sugar  early  becomes  available  and  may  be  oxidized  before  the 
nitrogen  belonging  to  it  is  eliminated,  or  if  the  sugar  be  formed 
in  excess,  it  may  be  stored  as  glycogen  in  the  liver  and  muscles 
of  the  body  for  subsequent  use.  In  this  way  it  is  obvious  that 
at  least  half  the  energy  in  protein  may  be  independent  of  the 
curve  of  nitrogen  elimination,  but  may  rather  act  as  though  it 
had  been  ingested  in  the  form  of  carbohydrate.  Carbohydrates 
when  ingested  do  not  cause  a  rise  in  the  production  of  heat, 
but  may  simply  undergo  oxidation  as  needed  by  the  cells.  This 
will  be  explained  in  the  next  chapter.  It  is  therefore  evident 
that  this  carbohydrate,  which  is  early  supplied  in  the  breaking 
down  of  protein,  may  distribute  its  energy  according  to  the  re- 
quirement of  the  cells  as  long  as  it  lasts.  This  is  apparently 
the  principal  cause  of  the  evenness  of  the  carbon  dioxid  excre- 
tion as  contrasted  with  the  great  irregularity  of  the  nitrogen 
elimination  after  protein  ingestion. 

It  has  been  noted  that  Frank  and  Trommsdorf,  and  Rubner 

1  Berger:  Inaugural  Dissertation,  Halle  (Nebelthau),  1901 ;  cited  from  Maly's 
"  Jahresbericht  tiber  Thierchemie,"  Bd.  xxxi,  p.  848. 


THE  INFLUENCE  OF  PROTEIN  FOOD. 


^33 


also,  in  experiments  previously  mentioned,  calculated  the  heat 
production  during  the  first  few  hours  after  feeding  with  meat  ac- 
cording to  the  usual  method  from  the  data  furnished  by  the 
nitrogen  and  carbon  elimination.  This,  however,  will  not  tell 
the  exact  truth  regarding  the  fat  and  protein  metabolism  during 
a  short  period,  for  dextrose  from  protein  may  be  undergoing 
oxidation  which  is  not  indicated  by  the  nitrogen  excretion  of  the 
time.  The  error  here  introduced  would  not  be  large,  but  a 
correction  would  tend  to  reduce  somewhat  the  calculated  heat 
production  during  the  period  immediately  following  the  ingestion 
of  meat.  This  experiment  should  be  controlled  by  simultaneous 
measurements  with  an  animal  calorimeter.  It  is  obvious  that 
respiration  experiments  extending  over  a  few  hours  cannot  so 
accurately  present  the  picture  of  the  metabolism  after  feeding 
with  meat  as  they  do  in  the  case  of  stan-ation,  where  the  inter- 
mediary' metabolism  is  a  constant  and  even  factor. 

Concerning  the  intermediate  metabolism  of  protein,  it  is 
further  shown  by  the  work  of  Parker  and  Lusk^  that  the  in- 
gestion of  casein  by  rabbits  maintained  under  the  influence  of 
benzoic  acid  results  in  an  elimination  of  hippuric  acid  which  is 
proportional  to  the  protein  metabolism.  This  is  illustrated  in 
the  following  table : 


CONSTANT    RELATION    BETWEEN    GLYCOCOLL   PRODUCTION 
AND    N    ELIMINATION    AFTER    INGESTING    PROTEIN. 


Day. 

Casein 

Ingested 

IN 

Grams. 

Benzoic 
Acid 

GIVEN  IN 

Grams. 

Grams 
Hippuric 
Acid  Ex- 
creted. 

Total  N 
Excreted 
IN  Grams. 

Hippuric 
Acid  N: 
Total  N. 

First 

4 

5 

lO 

I 
I 
1-5 

.7230 

•7575 
1.0302 

1.469 
1.456 
1.929 

I  :  25.9 

Second 

Third 

I  :  24.6 
I  :  23.9 

The  total  nitrogen  and  hippuric  acid  outputs  maintain  the 
same  ratio  throughout  the  above  experiment. 

It  may  be  estimated  that  under  these  conditions  the  metabo- 

'  Parker  and  Lusk:  "American  Journal  of  Physiology,"  igoo,  vol.  ill,  p.  472. 


134  SCIENCE   OF  NUTRITION. 

lism  of  protein  within  the  organism  yields  3.45  per  cent,  of 
glycocoll  as  compared  with  3.98  per  cent,  obtained  when  body 
protein  metabohzes  in  starvation  (p.  71).  This  experiment 
seems  remarkable  because  the  chemist  has  not  been  able  to  ob- 
tain glycocoll  from  casein,  and  it  may  be  quite  possible  that  only 
a  small  part  of  the  casein  given  was  really  digested  and  ab- 
sorbed. 

These  results  become  very  striking  in  the  light  of  the  work  of 
Abderhalden,  Gigon,  and  Strauss,  ^  which  shows  that  100  grams 
of  the  protein  matter  composing  the  rabbits'  body  may  yield  3.27 
grams  of  glycocoll. 

Magnus-Levy^  finds  that  25  to  27  per  cent,  of  the  total  urinary 
nitrogen  of  rabbits  fed  with  cream  and  of  a  goat  fed  with  hay 
is  excreted  in  the  form  of  hippuric  acid.  He  calculated  that 
only  4  per  cent,  of  this  could  have  been  derived  from  glycocoll 
preformed  in  the  protein  metabolized,  but  that  20  per  cent,  could 
have  originated  from  leucin  in  passing  through  a  glycocoll  stage. 
Brugsch  ^  finds  that  after  the  ingestion  of  benzoates  in  dogs  and 
men  not  over  three  per  cent,  of  the  total  nitrogen  appears  as 
hippuric  acid,  which  is  the  equivalent  of  a  production  of  2.5 
grams  of  glycocoll  from  protein.  Why  Parker  and  Lusk 
obtained  the  4  per  cent,  elimination  and  Magnus-Levy  secured 
one  of  25  per  cent,  is  not  at  present  clear. 

It  has  already  been  stated  that  the  individual  amino-acids 
lose  their  nitrogen  at  the  first  step  in  their  metabolism.  Only 
by  union  of  its  nitrogen  atom  with  benzoic  acid  (see  p.  71)  is 
glycocoll  spared  this  fate.  One  might  believe  that  other  amino- 
acids  might  unite  with  benzoic  acid  after  a  similar  fashion  and 
then  be  converted  into  hippuric  acid  by  oxidation  of  the  rest 
of  their  carbon  chains.     However,  Magnus-Levy^  found  that 

^Abderhalden,  Gigon,  and  Strauss:  "  Zeitschrif  t  f  iir  physiologische  Chemie," 
1907,  li,  p.  321. 

^Magnus-Levy:    "Miinchener  med.  Wochenschrift,"  1905,  Bd.  lii,  p.  2168. 
^Brugsch:    "  Centralblatt  fur  Physiol,  und  Path,  des  Stoffwechsels,"  1907, 
Bd.  viii,  p.  529. 

*  Magnus-Levy :    "  Biochemische  Zeitschrift,"  1907,  vi,  p.  541. 


THE  INFLUENCE  OF  PROTEIN  FOOD.  135 

benzoylated  compounds  of  alanin,  valin,  leucin,  phenylalanin, 
aspartic  acid,  glutamic  acid,  orinthin,  and  serin  when  admin- 
istered subcutaneously  could  not  be  changed  into  hippuric  acid 
by  the  organism  but  were  eliminated  in  the  urine.  No  theoretical 
explanation  can  be  given  for  the  large  quantity  of  hippuric  acid 
which  he  found  in  goat's  urine. 

The  writer  unsuccessfully  endeavored  to  bring  about  an 
elimination  of  cystin,  the  sulphur-containing  compound  in  the 
protein  complex,  by  constant  treatment  of  a  dog  with  benzol 
chlorid.  The  matter  was  then  taken  up  by  Wolf,  ^  who  has 
shown  that  after  frequent  administration  of  benzol  bromid  to  a 
dog,  an  artificial  cystinuria  is  brought  about.  The  benzol 
bromid  unites  with  the  cystin  liberated  in  protein  metabolism 
and  the  compound,  a  mercapturic  acid,  is  eliminated  in  the  urine. 
In  this  way  Wolf  increased  fourfold  the  unoxidized  sulphur 
(cystin-S)  in  the  urine,  and  nearly  removed  all  the  inorganic 
sulphate  from  the  urine,  although  curiously  enough  there  was 
a  slight  increase  in  the  quantity  of  ethereal  sulphates  present. 
Folin  and  Alsberg^  investigated  a  case  of  cystinuria  and  found 
similar  relations.  The  increase  in  neutral  sulphur  was  at  the 
expense  of  alkaline  sulphate  in  the  urine.  The  cystin  elimina- 
tion was  increased  by  increasing  the  protein  in  the  food. 

Thiele^  has  experimented  on  a  cystinuric  patient  and  finds  the 
same  quantity  of  cystin  in  the  urine  whether  the  patient  be 
starving  or  fed  with  carbohydrates,  with  meat,  or  with  the 
cystin  which  he  has  himself  excreted.  Since  the  cystin  of  meat 
and  that  obtained  from  his  own  excreta  (which  existing  in  his 
blood  he  could  not  burn)  were  nevertheless  destroyed  when 
ingested  by  way  of  mouth,  Thiele  argues  that  the  seat  of  this 
destruction  must  have  been  the  intestinal  mucosa,  to  which 
locality  modern  theory  more  and  more  attributes  the  process  of 
deamination  (see  p.  i88). 

*  Mariott  aad  Wolf:   "American  Medicine,"  1905,  vol.  ix,  p.  1026. 

*  Folin  and  Alsberg:  "American  Journal  of  Physiology,"  1905,  vol.  xiv,  p.  54. 

*  Thiele:   "Journal  of  Physiology,"  1907,  xxxvi,  p.  68. 


136  SCIENCE    OF   NUTRITION. 

Friedmann^  shows  that  the  cystin  of  mercapturic  acid  is  the 
same  cystin  as  may  be  obtained  on  the  cleavage  of  protein  in  the 
laboratory. 

If  cystin  be  administered  to  a  normal  person  it  is  burned  and 
does  not  alter  the  normal  relation  between  oxidized  and  unox- 
idized  sulphur  in  the  urine.^  Therefore  cystin  administered 
alone  gives  the  same  end-products  as  when  it  is  administered  in 
the  protein  complex. 

That  cystin  is  the  mother  substance  of  the  taurin  of  the  bile 
Friedmann^  illustrates  in  accordance  with  the  following  formulae : 
c  H2  SH  C  H2  SO3  H  CH2SO3H 

CHNH2  +  30  =  CHN  H2  —  CO,  -=  C  H2  N  Hj 

I  I 

C  OOH  COOH 

Cystin.  Cystinic  acid.  Taurin. 

The  indications  are  that  cystin  is  a  normal  product  of  pro- 
tein metabolism  which  a  patient  suffering  from  cystinuria  is 
unable  to  oxidize. 

In  a  phenomenon  called  alcaptonuria  tyrosin  and  phenyl- 
alanin  are  oxidized  only  as  far  as  the  alcaptonic  acids,  which  are 
uroleucinic  and  homogentisic  acids,  and  in  this  form  they  appear 
in  the  urine.  Their  production  from  phenylalanin  according 
to  Falta*  is  as  follows : 


l^OH  ^OH 


CH2  CH2 

1  I 

CHNH2       CHOH       CHOH       COOH 

COOH       COOH       COOH 

Phenylalanin.       Phenyl-a-lactic  acid.        Uroleucic  acid.       Homogentisic  acid. 

He  finds  that  if  phenylalanin  or  tyrosin  is  administered  in 

^  Friedmann:   "Hofmeister's  Beitrage,"  1904,  Bd.  iv,  p.  486. 

^  Blum:  Ibid.,  1904,  Bd.  v,  p.  i. 

^  Friedmann:  Ibid.,  1902,  Bd.  iii,  p.  i. 

*Falta:   "Biochemisches  Centralblatt,"  1904,  Bd.  iii,  p.  175. 


»        THE  INFLUENCE  OF  PROTEIN  FOOD.  137 

alcaptonuria,  each  is  completely  converted  into  the  alcaptonic 
acids  and  so  eliminated.  In  alcaptonuria  the  ratio  between 
homogentisic  acid  and  nitrogen  elimination  in  the  urine  is 
constant,  being  45  :  100/  while  the  distribution  of  the  various 
other  nitrogenous  compounds  in  the  urine  remains  normal. 
Garrod  and  Hale-  find  the  same  ratio  as  above,  and  believe  with 
Falta  that  where  this  deviation  from  normal  metabolism  occurs 
it  is  complete  in  the  sense  that  the  homogentisic  acid  excreted 
represents  the  whole  of  the  tyrosin  and  phenylalanin  of  the  pro- 
teins broken  do\Mi.  For  the  normal  fate  of  these  substances 
see  p.  293. 

Neubauer  and  Falta^  have  recently  emphasized  the  idea  that 
the  alcaptonic  acids  are  always  formed  in  normal  metabolism, 
but  in  this  rare  disease  cannot  be  further  oxidized.  The  power 
to  split  the  benzol  ring  is  absent.* 

Sugar,  glycocoll,  cystin,  and  the  alcaptonic  acids  are  there- 
fore products  of  protein  metabolism  the  excretion  of  which  may 
be  brought  about  by  special  means  or  by  certain  pathological 
conditions. 

Kynurenic  acid,  which  is  regularly  found  in  dogs'  urine,  has 
acquired  new  interest  since  Ellinger's^  discovery  that  if  a  dog  be 
given  tryptophan — a  product  of  proteolysis — the  kynurenic  acid 
is  greatly  increased  in  the  urine.  Mendel  and  Jackson*  found 
that  the  kynurenic  acid  elimination  in  dogs  varied  directly  with 
the  protein  metabolism,  but  was  not  derived  from  gelatin  metabo- 
lism. Ellinger''  has  fed  a  rabbit,  whose  urine  normally  contains 
no  kynurenic  acid,  with  tryptophan,  and  found  kynurenic  acid  in 

*  Langstein  and  Meyer:  "Deutsches  Archiv  fiir  klin.  Med.,"  1903,  Bd. 
Ixxviii;   Schumm:  "Miinchencr  med.  Wochenschrift,  "1904,  Bd.  xxxvi,  p.  1599. 

^  Garrod  and  Hale:   "Journal  of  Physiology,"  1905,  vol.  xxxili,  p.  205. 

^Neubauer  and  Falta:  "Zcitschrift  fiir  physiologische  Chemie,"  1904, 
Bd.  xlii,  p.  8i. 

^Neubauer:  "Deutsches  Archiv  fiir  klinische  Medizin,"  1909,  Bd.  xcv, 
p.  211. 

'  Ellingcr:   "Zcitschrift  fiir  Physiologische  Chemie,"  1904,  Bd.  xliii,  p.  325. 

'Mendel  and  Jackson:  "American  Journal  of  Physiology,"  189S,  vol.  ii, 
p.  I.     Consult  al.so  Mendel  and  Schneider:  Ibid.,  1901,  v,  p.  427. 

'  Ellinger:   Loc.  cil. 


138 


SCIENCE    OF   NUTRITION. 


the  urine.  Rabbits,  however,  normally  burn  kjnurenic  acid 
when  ingested  in  small'amounts.  He  reaches  the  conclusion  that 
animals  in  general  may  produce  k}Tiurenic  acid  from  trj^tophan 
in  protein  metabolism,  and  that  this  is  usually  readily  oxidized, 
except  in  the  organism  of  the  dog,  where  it  is  only  partly  destroyed 
and  therefore  appears  in  the  urine. 

The  study  of  creatinin  and  creatin  as  excretory  products  has 
recently  been  stimulated  by  the  discovery  by  Folin  of  a  quick 
and  relatively  accurate  method  of  determination. 

He  has  given  a  diet  of  milk,  cream,  and  carbohydrate  which 
is  free  from  creatinin  and  the  purin  bases,  and  has  noted  the 
effect  of  high  and  low  protein  content  of  the  diet  on  the  com- 
position of  human  urine. 

One  of  Folin' s^  experiments  may  thus  be  tabulated,  per- 
centages being  rendered  in  black  t}^e  (see  Appendix,  p.  364). 


INFLUENCE  OF  HIGH  .AND  LOW  PROTEIN  DIETS  ON  THE  RELA- 
TIA^  AMOUNTS  OF  THE  NITROGENOUS  CONSTITUENTS 
OF  THE  URINE. 


Food. 


Composition  of  the  Ueine  in  Grams. 


In  Grams. 


In  Cal- 
ories. 


Total 

N. 


Protein,  118  =  19 

Fa?-x-;8:::::::::i[^786 16.8 

Carb.,  225 


Protein,  6  =  i  N . . 

Fat,  52 1  [.2153 

Garb.,  400 


3-6 


Urea 

N. 


14.70 

87.5% 


2.20 
61.7% 


Ammo- 
nia 

N. 


0.49 
3.0% 


0.42 
11.3% 


Uric 
Acid 

N. 


o.i» 
1.1% 


0.09 
2.5% 


Creatinin 

N. 


0.58 
3.6% 


0.60 
17.2% 


Unde- 
termined 

N. 


0.85 
4.9% 


0.27 
7.3% 


A  study  of  this  table  will  reveal  the  fact  that  if  a  man  ingest 
a  diet  containing  a  medium  amount  of  protein,  and  again  one 
that  is  nearly  free  from  protein,  the  difference  in  the  character 
of  the  urine  in  the  two  cases  is  almost  exclusively  due  to  a 
diff'erence  in  the  output  of  urea.     The  quantity  of  creatinin 

^  Folin:  "American  Journal  of  Physiolog}',"  1905,  vol.  xiii,  p.  117. 


THE  INFLUENCE  OF  PROTEIN  FOOD. 


139 


eliminated  remains  independent  of  the  quantity  of  protein 
metabolized,  and  the  same  thing  holds  true  as  a  rule  for  uric 
acid  (see  p.  344).  This  led  Folin  to  distinguish  between  an 
endogenous  protein  metabolism  which  resulted  in  the  constant 
and  even  production  of  creatinin  and  uric  acid  and  was  a  mani- 
festation of  cell  metabolism,  and  an  exogenous  protein  metabolism 
as  represented  by  the  urea  elimination  which  is  in  greater  part 
derived  from  ingested  protein. 

The  creatinin  elimination  is  not  influenced  by  muscular 
work^  nor  by  the  increased  metabolism  of  body  proteins  which 
follows  phosphorus  poisoning  in  fasting  dogs.^  If  creatinin  be 
administered  in  the  food  it  is  largely  eliminated  in  the  urine.^ 

Fresh  muscle  substance  contains  creatin  and  never  creatinin.* 
The  production  of  creatinin  from  creatin  has  never  been  demon- 
strated, and  the  reverse  reaction  has  lately  been  suggested. 
Mellanby  finds  that  creatinin  is  not  excreted  by  young  chickens 
until  one  week  after  hatching,  that  is,  not  until  after  the  muscles 
are  saturated  with  creatin.  Creatin  is  absent  from  the  urines  of 
young  children.^  The  reason  for  this  may  be  that  the  creatinin 
formed  in  metabolism  is  converted  into  creatin  for  the  upbuild- 
ing of  new  tissue.  Other  investigators,^  however,  have  found 
small  quantities  of  creatinin  in  the  urine  of  breast-fed  infants 
during  the  first  week  of  their  lives.  The  chemical  reaction  would 
be  as  follows: 


N(CH3).CH2  NCCHg) .  CHjCOjH 

C  =  NH 
\ 

NH C  =  0  N  Hj 

Creatinin.  Creatin. 


/ 
+  II,  O  =         C  =  NH 

\ 


'  Hoogenhuyze   and   Verplocg:    "Zeitschrift   fur   physiologische    Chemie," 
1905,  vol.  xlvi,  p.  415. 

'  Lusk:    "American  Journal  of  Physiology,"  1907,  vol.  xix,  p.  461. 
'  Folin:   " Hammarsten's  Festschrift,"  1906,  iii,  p.  10. 
*  Mellanby:  "Journal  of  Physiology,"  1908,  vol.  xxxvi,  p.  447. 
•Rietschel:   "Jahrbuch  fur  Kinderheilkunde,"  1905,  Bd.  xli,  p.  4. 
•Ambcrg  and  Morrill:    "Journal  of  Biological  Chemistry,"  1907,  vol.  iii, 
P-  3"-. 


I40  SCIENCE    OF   NUTRITION. 

Normal  urine  never  contains  creatin.  It  is  not  a  product 
of  the  endogenous  metabolism.  When  ingested  it  may  be 
destroyed  or  be  eliminated  in  the  urine,  but  is  never  converted 
into  creatinin.^ 

In  cases  where  body  protein  is  metabdlized,  such  as  fasting, 
phosphorus  poisoning,^  carcinoma  of  the  liver,^  during  the  period 
of  involution  of  the  uterus  after  parturition*  and  also  immedi- 
ately before  parturition,^  creatin  appears  in  the  urine  as  an 
index  of  the  breakdown  of  muscle  tissue. 

Mellanby  concludes  from  the  absence  of  creatin  in  the 
cross-striated  muscle  of  the  lobster  that  it  is  not  essential  either 
for  muscle  contraction  or  response  to  nerve  impulses.  He  finds 
that  muscular  contraction  is  without  influence  on  the  creatin 
content  of  a  muscle. 

Much  work  and  speculation  have  centered  around  the  origin 
of  creatinin  without  any  certainty  of  result. 

Creatin  is  the  extractive  existing  in  larger  quantity  than  any 
other  in  muscle.  In  the  process  of  manufacture  of  Liebig's 
extract  of  beef  it  is  largely  converted  into  creatinin.  Such  an 
extract,  which  contains  also  xanthin,  is  not  strictly  a  food,  since 
its  constituents  are  largely  ready  for  elimination  in  the  urine.® 
Biirgi'^  shows  that  if  meat  extract  be  administered  it  is  excreted 
in  the  urine  excepting  4.57  per  cent,  of  its  nitrogen,  14.85  per 
cent,  of  its  carbon,  and  17.55  P^^  cent,  of  its  energy  content. 

Its  value  lies  in  its  flavor,  which  promotes  the  proper  flow 
of  the  digestive  juices.^ 

It  may  be  incidentally  remarked  that  the  principal  value  of 
many  "patent"  foods,  "invalid"  foods,  etc.,  lies  in  their  flavor. 

^Folin:   "Hammarsten's  Festschrift,"  1906,  iii,  p.  i. 

^Lefmann:   " Zeitschrif t  f iir  physiologische  Chemie,"  1908,  Bd.  Ivii,  p.  476. 
^  Hoogenhuyze  and  Verploeg:   Ihid.,  igo8,  Bd.  Ivii,  p.  161.     Also  Mellanby, 
loc.  cit. 

*  Shaffer:   "American  Journal  of  Physiology,"  1908,  vol.  xxiii,  p.  14. 
'Murlin:   "American  Journal  of  Physiology,"  1909,  vol.  xxiii,  p.  xxxi. 
^  Rubner:   "  Zeitschrif t  fiir  Biologic,"  1883,  Bd.  xix,  p.  343. 
'  Biirgi:   "  Archiv  fiir  Hygiene,"  1904,  Bd.  li,  p.  i. 
^Voit:    " Stoffwechsel,"  1882,  p.  449. 


THE  INFLUENCE  OF  PROTEIN  FOOD. 


141 


If  agreeable  to  the  taste  of  the  individual  they  usually  afford  a 
harmless  indulgence.  That  beef,  milk,  cream,  butter,  and  rice 
are  equally  suitable  for  all  the  purposes  of  proper  living  is  a 
fact  not  sufficiently  advertised.  The  old-time  fraud  of  "patent " 
foods  being  "brain  restorers"  is  as  foolish  a  lie  as  can  be  written. 
Rubner^  says  that  the  rise  of  the  curve  of  sulphur  elimination 
precedes  that  of  nitrogen,  while  that  of  the  phosphate  elimination 
follows  it.  (See  also  p.  126.)  The  experiment  is  on  the  dog 
already  described  (page  127)  during  the  six-hour  periods  follow- 
ing an  ingestion  of  460  grams  of  washed  meat.  The  follow- 
ing represents  the  percentage  elimination  of  nitrogen,  sulphur, 
and  phosphorus  during  six-hour  intervals  on  the  third  feeding 
day.     Of  100  per  cent,  there  were  excreted: 


N. 

During  the  first       6  hours 24.8 

"       second  6     "      39-8 

"       third     6     "      23.6 

"       fourth  6     "      1 1.8 


S. 
36.7 

31-7 
21. 1 
10.5 


P2OS. 
16.0 
32.1 

33-4 

18.5 


Sherman  and  Hawk,^  however,  give  curves  showing  beauti- 
fully an  almost  parallel  elimination  of  sulphur  and  nitrogen  in 
man  on  a  mixed  diet.     A  curv^  showing  this  is  here  presented  : 


8     DAY 


240 


20a 


Fig.  8. — The  curves  here  shown  represent  the  relative  fluctuations  in  the 
average  rates  of  excretion  of  nitrogen  and  SO3.  The  values  on  the  left  repre- 
sent percentages  of  an  assumed  standard  rate  of  excretion  for  each  of  these  con- 
stituents. It  will  be  seen  that  in  general  the  excretion  of  sulphates  ran  quite 
closely  parallel  to  that  of  nitrogen. 

*  Rubner:   "Energiegesetze,"  1902,  p.  368. 

'  Sherman  and  Hawk:  "Am.  Jour,  of  Physiology,"  1900,  vol.  iv,  p.  43. 


142  SCIENCE    OF   NUTRITION. 

The  parallelism  of  the  hourly  curves  of  nitrogen  and  sulphur 
excretion  in  man  after  the  ingestion  of  veal  cutlets  is  shown  in 
the  curve  by  Wolf  on  p.  125. 

This  discussion  of  the  elimination  of  various  intermediary 
products  of  protein  metabolism  lifts  the  mist  from  many  factors 
sufficiently  to  give  an  outlook  over  a  field  of  increasingly  fruitful 
investigation. 

A  question  v^hich  has  aroused  great  interest  is  that  con- 
cerning the  production  of  fat  from  protein.  Pettenkofer  and 
Voit^  found  that  after  ingesting  considerable  quantities  of 
protein,  although  the  nitrogen  of  the  protein  was  eliminated  in 
the  urine,  a  part  of  the  carbon  was  retained  in  the  body  and 
not  excreted  by  the  usual  channels.  They  estimated  that  meat 
protein  contained  3.68  grams  of  carbon  to  each  gram  of  nitrogen. 
If  less  than  3.68  grams  of  carbon  appeared  in  the  total  excreta 
when  one  gram  of  nitrogen  was  eliminated,  then  some  pro- 
tein carbon  must  have  been  stored  in  the  body.  This  carbon 
might  have  been  retained  in  two  forms — as  glycogen  or  as  fat. 
Claude  Bernard  had  shown  that  glycogen  increases  in  the  liver 
after  the  ingestion  of  protein.  The  retained  carbon  as  ob- 
served by  Pettenkofer  and  Voit  was  in  such  large  quantity  as  to 
preclude  the  possibility  of  its  retention  entirely  as  glycogen,  and 
therefore  they  concluded  that  fat  must  have  been  prepared  from 
protein  and  stored  up  in  the  body.  This  afforded  an  experi- 
mental basis  for  the  theory  of  a  production  of  fat  from  protein 
in  fatty  degeneration. 

Later  Rubner,^  in  Voit's  laboratory,  showed  that  the  re- 
lation 3.68  C  :  I  N  in  protein,  as  used  by  Pettenkofer  and  Voit, 
was  inaccurate,  and  that  meat  fully  extracted  with  ether  contains 
only  3.28  of  carbon  to  one  of  nitrogen.  The  polemical  arraign- 
ment by  Pfiiiger^  of  Voit's  older  work  was  based  upon  these 

'Pettenkofer  and  Voit:  "Annalen  der  Chemie  und  Pharm.,"  1862,  II 
Supplement,  pp.  52  and  361. 

^  Rubner:  " Zeitschrif t  fiir  Biologie,"  1885,  Bd.  xxi,  p.  324. 

^Pfluger:   "Pfliiger's  Archiv,"  1892,  Bd.  lii,  p.  239, 


THE  INFLUENCE  OF  PROTEIN  FOOD. 


143 


results  of  Rubner.  Instead  of  there  being  a  great  retention  of 
protein  carbon,  there  was  none  in  some  experiments  and  very 
little  in  others.  The  formation  of  fat  from  protein  was  evidently 
less  easy  of  demonstration  than  it  had  seemed. 

The  subject  was  investigated  anew  by  Cremer/  who  starved 
a  cat  for  many  days,  and  then  gave  the  animal  all  the  lean  meat 
it  would  eat,  or  about  450  grams  a  day.  The  cat  was  kept 
in  a  respiration  apparatus  and  the  total  excreta  were  collected. 
The  carbon  belonging  to  the  meat  ingested  was  calculated  at  the 
low  ratio  of  3.18  to  i  of  nitrogen.  The  average  daily  metabolism 
during  the  eight  days  of  meat  ingestion  is  indicated  in  the 
following  table : 

Weights  in  Grams. 

Meat  C  calcu-  C    from    meat 

N  in  urine  C  in  lated   from  added  to  the 

and  feces,      Urine,     Feces,     Respiration,  N  excreted,  body, 

13-0  7-5  1-4  25.4  41.6  7.3 

34-3 

There  was  a  daily  excretion  of  13  grams  of  nitrogen  corre- 
sponding to  the  liberation  of  41.6  grams  (13  x  3.18)  of  protein 
carbon.  But  only  34.3  grams  of  carbon  were  actually  elimi- 
nated from  the  body,  and  a  difference  of  7.3  grams  was  re- 
tained in  the  body;  17.5  per  cent,  of  the  protein  carbon  there- 
fore was  not  eliminated.  For  eight  days  the  whole  carbon 
retention  was  58  grams,  which  corresponds  to  a  glycogen  produc- 
tion of  130  grams.  The  cat,  however,  contained  only  35  grams 
of  glycogen,  determined  after  killing  it  at  the  end  of  the  experi- 
ment.    The  balance  of  the  carbon  must  have  been  stored  as  fat. 

Cremer^  notes  that  a  cat  fed  as  above  contains  1.47  per  cent, 
of  muscle  glycogen,  which  is  as  much  as  the  maximum  (1.37 
per  cent.)  found  by  E.  Voit  in  geese  after  the  ingestion  of  starch. 

Since  it  is  known  that  sugar  in  excess  may  be  converted  into 
body  fat  and  that  meat  may  yield  58  per  cent,  of  sugar  in  metab- 
olism, there  is  every  reason  to  believe  that  if  protein  be  ingested 

'  Cremer:  "Zeitschrift  fiir  Biologic,"  1899,  Bd.  xxxviii,  p.  309. 
'  Cremer:  "Zeitschrift  fur  Biologic,"  1899,  Bd.  xxxviii,  p.  313. 


144 


SCIENCE    OF   NUTRITION. 


in  excess  this  sugar  may  be  converted  into  glycogen  and  then,  if 
the  quantity  be  sufficient,  into  fat. 

It  is  quite  possible  that  the  origin  of  fat  from  protein  is  in 
its  nature  the  same  as  the  origin  of  fat  from  carbohydrates. 

Rubner^  has  noted  a  similar  carbon  retention  after  the  inges- 
tion of  protein  in  excess.    Two  examples  of  this  may  be  cited. ^ 

The  first  experiment  was  upon  a  dog  which  had  been  reduced 
by  starvation  from  a  weight  of  ii  to  6  kilograms.  He  was  then 
given  500  grams  of  meat  a  day. 

CARBON  RETENTION  AFTER  PROTEIN  INGESTION. 


Day. 

Food. 

N  IN 

Ex- 
creta. 

C  from 
Fat  Meta- 
bolism. 

Calories 

from 
Protein. 

Calories 

FROM 

Fat. 

Total 
Cal. 

FROM 

Meta- 
bolism. 

Body 
Weight. 

First 

Second 

Third 

Fourth 

Starvation. 
Starvation. 
500  g.  meat. 
500  g.  meat. 

1-31 
1.52 

13-05 
14.20 

22.46 

19.77 

(-0.87) 

(-2.41) 

32-75 
38.00 

339-3 
355-0 

275.2 

243.2 

-8.9 

—24.9 

308.0 
281.2 
330-4 
330.1 

5-94 
5.82 
5-86 
6.00 

This  experiment  shows  that  on  the  first  day  of  meat  ingestion 
0.87  gram  of  carbon  from  protein  was  retained  in  the  dog  and  on 
the  second  day  2.41  grams  were  so  retained.  Rubner^  has 
calculated  that  the  carbon  in  the  respiration  derived  from  pro- 
tein has  a  calorific  value  of  10.2  calories  per  gram.  When  pro- 
tein carbon  is  retained  in  the  body,  its  heat  equivalent  must  be 
deducted  from  the  heat  value  of  the  protein  metabolism  as  com- 
puted from  the  nitrogen  in  the  excreta,  in  order  to  obtain  the 
true  total  of  heat  liberated.  This  heat  value  of  retained  carbon 
is  a  little  above  the  calorific  value  of  carbon  in  dextrose,  which 
is  9.4  calories  per  gram. 

The  second  experiment  which  may  be  cited  was  done  by 
Rubner  upon  a  large  dog  which  was  given  2000  grams  of  meat 
at  a  time.    The  results  were  as  follows : 

^  Rubner:   "Gesetze  des  Energieverbrauchs,"  1902,  pp.  57,  84. 

^  For  a  third  example  see  this  book,  table  on  p.  151. 

^  Rubner:  "Zeitschrift  fiir  Biologie,"  1885,  Bd.  xxi,  p.  363. 


THE    IXFLUE^XE    OF    PROTEIN    FOOD.  145 

CARBON  RETENTION  AFTER  PROTEIN  INGESTION. 


Food. 

Excreta. 

Calories. 

Kind. 

N. 

Cal. 

N. 

Fate. 

Protein. 

Fat. 

Total. 

First Starv. 

Second Starv. 

Third 1      2000  g. 

'       meat. 

Fourth ;       Starv. 

Fifth 2000  g. 

meat. 
Sixth Starv. 

68 
68 

1926 
1926 

5-01 

S-io 

51-60 

12.39 
52.68 

12.18 

48.19 

49-00 

(-29-58) 

,     37-19 
(-26.58) 

36.82 

I25-7S 
128.00 
1351-9 

325-62 
1380.22 

319-12 

592.72 

613-77 

— 305.66 

420.54 
—274-57 

452-89 

718.49 

741-77 

1046.34 

746.16 
1105.65 

772.01 

On  both  days  when  2000  grams  of  meat  were  ingested,  carbon 
was  retained  in  the  organism  either  as  glycogen  or  fat.  On  the 
first  of  these  days  17.7  per  cent,  of  the  total  protein  carbon  was 
retained,  which  corresponds  to  17.5  per  cent,  found  by  Cremer 
in  the  cat  during  a  prolonged  period  of  protein  diet.  The 
writer,  on  the  basis  of  his  work  on  diabetes,  computes  that  44 
per  cent,  of  the  total  carbon  in  meat  protein  may  be  converted 
into  dextrose  (p.  132).  It  is  known  that  sugar  is  convertible 
into  fat  (p.  175).  If  44  per  cent,  of  protein  carbon  may  be 
converted  into  dextrose,  and  under  other  conditions  17.5  per 
cent,  may  be  converted  into  fat,  it  is  evident  that  of  the  total 
dextrose-carbon  which  may  be  produced  in  protein  metabolism, 
40  per  cent,  can  be  converted  into  fat-carbon  (p.  175).  There 
seems  to  be  no  doubt  that  protein  may  in  part  be  converted 
first  into  glycogen  and  then  into  fat  after  excessive  protein 
ingestion. 

An  interesting  contribution  to  this  subject  has  been  made  by 
Weinland,^  who  found  in  the  case  of  the  blow-fly  {calliphora), 
which  lays  its  eggs  in  meat,  that  both  the  larvae  and  a  pulp  made 
by  crushing  them  had  the  power,  in  the  absence  of  oxygen,  to 
split  peptone  into  amino-acids,  deaminize  these  with  evolution 
of  ammonia,  and  then  with  evolution  of  carbon  dioxid  to  produce 
higher  fatty  acids,  presumably  through  synthetic  union  of  the 
acids  which  had  been  freed  of  their  amino  groups.     Such  a 

'  Wcinland:   "Zeitschrift  fiir  Biologic,"  1908,  Bd.  li,  ]>.  197. 


146  SCIENCE    OF   NUTRITION. 

procedure  reasonably  explains  the  formation  of  fat  from  protein 
in  the  sense  of  the  older  theories.     (See  p.  128.) 

The  question  of  a  "fatty  degeneration"  of  protein  under 
pathological  conditions  is  another  matter  and  will  be  considered 
in  another  place.     (See  Chapter  XII.) 

The  last  two  experiments  of  Rubner's  bring  to  light  a  very 
striking  change  in  the  metabolism  after  the  ingestion  of  protein 
in  excess.  The  total  heat  production  is  markedly  increased. 
To  what  may  this  be  due  ? 

Von  Mering  and  Zuntz^  believed  that  such  increased  metabo- 
lism was  due  to  the  activity  of  the  intestinal  tract  after  the  in- 
gestion of  food. 

Voit^  criticized  this  view  and  said  that  a  rise  in  the  carbon 
dioxid  excretion,  from  366  grams  in  starvation  to  783  grams 
after  ingestion  of  meat  in  excess,  was  too  great  to  be  due  to 
intestinal  activity,  and,  indeed,  corresponded  to  the  rise  noted 
only  after  the  hardest  exercise.  Furthermore,  Voit  had  shown 
that  after  giving  a  medium  quantity  of  fat,  the  carbon  dioxid 
excretion  and  oxygen  absorption  were  almost  the  same  as  in 
hunger,  notwithstanding  the  activity  of  the  filled  intestine. 

This  question  has  received  very  painstaking  and  elaborate 
investigation  at  the  hands  of  Rubner,  who  has  published  his 
results  in  a  book  entitled  "Die  Gesetze  des  Energieverbrauchs 
bei  der  Emahrung."  This  volume  is  an  extension  of  a  work  of 
which  a  preliminary  communication  was  published  by  Rubner^ 
from  Voit's  Munich  laboratory  in  1885.  During  subsequent 
years  of  continued  activity  the  doctrines  were  more  and  more 
firmly  established, 

Rubner  shows  that  bones  given  to  a  dog  will  not  increase  his 
metabolism,  in  spite  of  the  intestinal  irritation,  so  the  increase 
after  meat  ingestion  is  not  due  to  a  nerve  reflex  of  mechanical 


^  von  Mering  and  Zuntz:   "Pfluger's  Archiv,"  1877,  Bd.  xv,  p.  634. 

^Voit:    "Physiologic  des  Stoffwechsels,"  1881,  p.  209. 

^Rubner:    " Sitzungsberichte  d.  kgl.  bayr.  Acad.  d.  Wissenschaft,"    i88q, 
Heft  4. 


THE    INFLUENCE    OF    PROTEIN    FOOD.  147 

nature.  Further,  the  metaboHsm  is  not  raised  after  the  ingestion 
of  meat  extract,  so  the  chemical  stimulus  of  flavors  which  start 
activity  in  the  glands  does  not  affect  total  metabolism.  Again, 
the  ingestion  of  water  in  the  quantity  contained  in  meat,  while  it 
may  cause  a  rise  in  nitrogen  in  the  urine  followed  by  a  fall — the 
rise  being  due  to  a  rapid  washing  out  of  nitrogenous  decomposi- 
tion products — does  not  alter  the  total  metabolism  in  any  wav. 

The  absence  of  true  "intestinal  work"  or  "Darmarbeit"  in 
the  sense  of  Zuntz  is  further  shown  by  the  fact  that  Johansson^ 
has  given  a  fasting  man  75  grams  of  dextrose  without  the  slightest 
increase  in  the  output  of  carbon  dioxid.  If  dextrose  had  been 
consumed  the  carbon  dioxid  excretion  would  have  risen  (see  p. 
176),  therefore  dextrose  was  retained  as  glycogen.  Since  all 
these  processes  were  without  effect  on  the  carbon  dioxid  output 
it  follows  that  the  intestinal  activit'es  involved  did  not  cause  an 
increase  in  the  total  metabolism.  Of  similar  import  are  the 
results  by  the  same  writer  after  administering  50  grams  of 
dextrose  to  a  diabetic.  The  sugar  was  absorbed  and  eliminated 
in  the  urine  without  affecting  the  carbon  dioxid  output. 

Cohnheim^  has  employed  "fictitious  feeding"  in  a  case  of  a 
fasting  dog  with  an  esophageal  fistula.  The  dog  was  given  meat 
which  passed  through  the  fistula  without  reaching  the  stomach. 
Such  a  procedure  results  in  a  psychic  flow  of  gastric  juice,  which 
in  turn  starts  up  activity  in  the  digestive  glands  of  the  intestinal 
tract.  The  result  showed  an  increased  heat  production  of  9 
per  cent,  during  a  three-hour  period.  The  animal  had  been 
kept  at  an  environmental  temperature  of  t,^°.  There  was  no 
increase  in  the  protein  metabolism  and  the  "intestinal  work" 
was  therefore  accomplished  at  the  expense  of  the  fat  or  glycogen 
reserve.  Cohnheim  notes  that  if  the  above  increase  in  metabo- 
lism were  distributed  over  twenty-four  hours  it  would  amount 
to  only  I  per  cent,  of  the  total  energ>'  production,  and  would 

'  Johansson:   "Skandin.  Archiv  fur  Physiologic,"  1908,  Bd.  xxi,  p.  i. 
'  Cohnheim:   "Archiv  fiir  Hygiene,"  1906,  Bd.  Ivii,  p.  401. 


148  SCIENCE    OF   NUTRITION. 

not  explain  the  very  great  increases  in  metabolism  which  have 
been  noted  after  the  ingestion  of  meat  in  large  quantities. 

Rubner  determined  the  starvation  metabolism  during 
twenty-four  hours  and  used  this  as  a  unit  for  the  measurement  of 
the  absolute  "requirement"  of  the  organism.  This  "require- 
ment" of  energy  may  be  met  by  the  ingestion  of  an  equivalent 
"maintenance  diet"  which  covers  the  requirement.  An 
"abundant  diet"  contains  a  larger  amount  of  potential  energy 
than  the  organism  requires. 

Rubner  at  first  found  that  if  the  food  ingested  had  a  lower 
calorific  value  than  the  body's  requirement,  then  the  metabolism 
was  not  usually  increased  after  the  ingestion.  This  is  illus- 
trated in  one  of  his  earlier  experiments^  summarized  below. 

Food.  Metabolism  in  Calories. 

Starvation 867 

Bones,  40  grams 812 

Meat,  720  grams 836 

Meat,  760  grams 875 

So  if  the  food  contains  less  than  the  energy  requirement,  the 
metabolism  may  not  be  increased  in  spite  of  activity  of  the 
glands  and  muscles  of  the  intestinal  tract. 

To  explain  this  Rubner^  introduced  his  compensation  theory. 
This  assumed  a  certain  reciprocity  between  the  muscles  and  the 
glands.  During  starvation  and  medium  temperature,  a  great 
part  of  the  body's  heat  is  produced  in  the  muscles,  and  those 
cells  ordinarily  concerned  in  taking  up  food  are  quiet  and  pro- 
duce little  heat.  On  warming  the  outside  air  the  amount  of 
metabolism  in  the  muscles  decreases.  The  same  thing  may  take 
place  when  gland  cells  and  intestinal  musculature  are  thrown 
into  activity;  the  voluntary  muscles  are  proportionally  relieved 
from  the  necessity  of  heat  production  for  the  maintenance  of 
body  temperature  through  chemical  regulation. 

Quite  a  different  picture  is  presented  when  an  abundant 
diet  is  supplied  to  the  dog.     If  protein  above  the  calorific  re- 

^  Rubner:   "Zeitschrift  fiir  Biologie,"  1883,  Bd.  xix,  p.  349. 
^  Rubner:  "Die  Gesetze  des  Energieverbrauchs,"  1902,  p.  8. 


THE  INFLUENCE  OF  PROTEIN  FOOD.  149 

quirement  be  ingested  there  is  a  very  considerable  rise  in  the 
heat  production.  This  increase  is  greater  in  the  case  of  protein 
than  with  any  other  foodstuff.  Rubner  calls  this  action  of 
abundant  protein  food  in  raising  the  metabolism  the  specific 
dynamic  action  of  protein.  This  action  is  shown  in  the  two 
experiments  of  Rubner  cited  on  pages  144,  145.  In  the  second 
experiment,  the  total  metabolism  during  the  starvation  days  is 
as  follows: 

First  day 718.5  calories. 

Second  day 741.8       " 

Third  day 746.2       " 

Fourth  day 772.0       " 

Rubner  took  the  average  of  the  last  two  days  as  representing 
the  requirement  in  starvation,  or  759.1  calories.  After  admin- 
istering 2000  grams  of  meat  containing  1962  calories,  or  the  full 
starvation  requirement  and  153.7  per  cent,  besides,  the  heat 
production  rose  from  759.1  calories  per  day  to  1046.34  and 
1105.65  calories,— that  is,  it  increased  42.2  and  45.6  per  cent. 
Rubner  recalculated  the  calories  produced  by  the  metabolism 
during  the  experiment  on  the  assimiption  that  the  carbon  from 
protein  was  retained  as  glycogen  and  not  as  fat,  and  in  this  way 
estimated  the  increased  metabolism  after  this  ingestion  of  meat 
at  45.5  and  48.7  per  cent,  above  the  starvation  minimum. 

Combining  the  results  of  such  experiments,  Rubner^  finds 
the  following  increasing  specific  dynamic  effect  of  protein  as 
the  quantity  above  the  day's  requirement  becomes  larger. 

Excess  above  Increase  in  Heat 

Requirement.  Production. 

56  per  cent 19  per  cent. 

9°         ;;        35       " 

^°5  44       " 

'S3  49       " 

Here  were  increases  in  total  metaboli.sm  comparable  to  those 
induced  by  considerable  mechanical  work.     The  body  metabo- 
'  Rubner:  "Gesetze  des  Energieverbrauchs,"  p.  90. 


150  SCIENCE    OF   NUTRITION. 

lized  in  largely  increased  measure  without  doing  any  external 
work. 

A  more  rapid  respiration  alone  betokened  the  increased 
oxidation  and  the  effort  of  the  body  to  rid  itself  of  excess  of  heat 
through  physical  regulation.  The  temperature  of  the  dogs 
scarcely  changed,  so  perfect  is  the  regulatory  mechanism  for 
the  discharge  of  heat.  Thus  in  one  dog  the  temperature  was 
38.16°  before  the  meal,  38.74°  during  the  digestion,  and  38.17° 
at  the  end  of  digestion. 

Rubner  differentiated  between  three  stages  of  protein  metab- 
olism. First,  in  the  cases  of  undernutrition  and  of  mainte- 
nance diet  in  which  protein  enters  into  the  circulation  and  spares 
an  isodynamic  quantity  of  the  body  substances;  second,  the 
stage  of  abundant  nutrition  where  the  protein  raises  the  metab- 
olism through  its  specific  dynamic  power;  third,  an  intermediary 
stage  where  protein  may  be  added  as  tissue  to  the  body  without 
increasing  the  metabolism.  This  period  of  "pure  deposit"  of 
tissue  may  rapidly  pass  into  the  stage  of  deposit  united  with 
specific  action  causing  increase  in  heat  production.  It  will  be 
apparent  later  that  the  first  and  third  stages  of  protein  nutrition 
can  be  achieved  only  at  low  or  medium  temperatures  of  environ- 
ment. 

An  example  of  the  stage  of  the  deposit  of  protein  tissue 
without  a  rise  in  metabolism  is  given  by  Rubner^  as  follows : 

Calories 
N  TO  Body.  per  Kg. 

Starvation 45-6i 

Starvation 43-26 

Meat +  8.7  44.48 

Meat +  4-7  46.16 

This  kind  of  growth  of  tissue  without  a  corresponding  rise 
in  metabolism  takes  place  in  the  normal  adult  only  when  the 
protein  ingested  is  below  the  heat  value  of  the  fasting  metabo- 
lism.    If,  however,  a  larger  quantity  of  protein  be  ingested  than 

^  Rubner:   "Gesetze  des  Energieverbrauchs,"  p.  256. 


THE  INFLUENCE  OF  PROTEIN  FOOD,  151 

the  heat  requirement  of  the  body  calls  for,  then  the  usual 
specific  dynamic  action  occurs  and  also  a  continued  "secondary" 
rise  in  total  day-to-day  metabolism,  which  increases  as  long  as 
protein  is  deposited.  \Vhen  nitrogen  equilibrium  is  established 
the  heat  production  remains  constant  at  a  higher  level. 

Rubner^  illustrates  this  important  fact  in  the  following  ex- 
periment on  a  dog : 

Calories  in  Total  Calories  of 

Meat  Ingested.  N  to  Body.        Carbon  to  Body.        Metabolism. 

°     —1-31  •  ■•  310.61 

o    —1-52  ...  278.00 

4fi-5 3-95  2.97  311.43 

40I-5 2.80  3.70  333-82 

481.5 2.30  1. 61  368.41 

4^1-5 2.20  2.53  361.70 

4°i-S 0.92  4.45  375.47 

4^^-5 0-20  4.31  395-77 

°    —3-70  -  ..  357-20 

°    — 2.64  ...  310.29 

The  constant  deposit  of  protein  therefore  continually  raises 
the  heat  production  in  the  organism  until  a  point  is  reached 
when  no  more  protein  is  added  to  the  body.  This  is  the  point 
of  nitrogenous  equilibrium,  and  is  very  quicldy  attained.  It 
is  evident  that  on  a  purely  protein  diet  no  great  addition  of 
protein  tissue  can  usually  take  place  in  the  adult  on  account  of 
this  secondary  dynamic  action.  (Compare  with  Bornstein's 
work,  p.  no.) 

Rubner  shows  that  the  retention  of  fat  from  protein  in  the 
body  has  nothing  to  do  with  this  action.  Protein  retention  is 
much  more  readily  brought  about  on  a  mixed  diet  containing 
large  quantities  of  carbohydrates,  as  will  be  seen  in  a  subsequent 
chapter. 

Thus  far  in  this  book  the  influence  of  external  temper- 
ature upon  the  course  of  protein  metabolism  has  not  been 
discus.sed.  Rubner  has  shown  that  this  is  a  factor  of  profound 
significance.     It  has  already  been  demonstrated  how,  through 

'  Rubner:   "Die  Gesetzc  des  Energieverbrauch.s,"  1902,  p.  246. 


152 


SCIENCE   OF  NUTRITION. 


chemical  regulation,  the  basal  requirement  of  the  body  is  reflexly 
increased  by  increasing  cold  in  the  environment.  Rubner^ 
compared  the  starving  metabolism  of  a  dog  at  different  tem- 
peratures with  that  of  the  same  dog  when  loo,  200,  and  320 
grams  of  meat  were  ingested.  The  results  are  presented  as 
follows  in  terms  of  calories  produced  per  kilogram  of  body 
weight : 

INFLUENCE  OF  EXTERNAL  TEMPERATURE  ON  METABOLISM 
AFTER  PROTEIN  INGESTION. 


Temperature. 


7' 
15 
20 

25 
30 


Starvation. 


86.4 
63.0 

55-9 
54-2 
56.2 


100  Gm.  Meat 

OR  24  Cal. 

PER  Kg. 

55-9 
55-5 
55-6 

200  Gm.  Meat 
OR  48  Cal. 
PER  Kg. 


77-7 

57-9 
64.9 

63-4 


320  Gm.  Meat 

OR  81  Cal. 

PER  Kg. 


87.9 
86.6 
76.3 

83-0 


One  hundred  grams  of  meat  did  not  change  the  metabolism 
at  20°,  25°,  or  30°;  200  grams  of  meat  had  no  effect  at  20°  or  at 
7°,  but  at  25°  and  at  30°  there  was  an  increase,  although  the 
food  contained  fewer  calories  than  the  requirement.  With  320 
grams  of  meat  there  was  a  great  increase  above  the  starvation 
requirement,  except  at  7°,  where  it  is  a  maintenance  diet  and  the 
metabolism  remains  unchanged.  In  other  words  at  a  tem- 
perature of  30°  the  specific  dynamic  action  of  this  amount  of 
protein  is  capable  of  increasing  the  heat  production  above  that 
of  starvation  by  about  53  per  cent.,  while  at  7°  there  is  no 
change  whatever.  It  is  also  evident  that  at  a  high  temperature 
even  a  small  quantity  of  protein  such  as  200  grams  of  meat 
causes  a  considerable  rise  of  metabolism. 

Rubner  gives  the  metabolism  in  terms  of  calories  per  kilo- 
gram after  the  ingestion  of  550  grams  of  meat  or  173.8  calories 
per  kilogram  of  body  weight  in  a  dog,  as  follows : 

^  Rubner:  Ibid.,  p.  109. 


THE    INFLUENCE    OF    PROTEIN   FOOD.  1 53 

Temperature.  Starvation.  550  Grams  Meat.  Incre.'^se. 

4.2° 128. 1  133-5  4.2  per  cent. 

14.5° 100.9  1 1°-9  9-9        " 

22.1° 70.7  loi.o  42.0        " 

30.7° 62.0  117. 2  89.0        " 

These  experiments  make  evident  the  extraordinary  influence 
of  variations  in  the  surrounding  temperature  on  the  metaboKsm 
when  the  same  quantity  of  meat  is  given.  The  influence  of  tem- 
perature must  therefore  be  continually  kept  in  mind  as  a  most 
important  factor  of  the  amount  of  the  metabolism.  Many  ex- 
periments reported  as  having  been  done  at  the  "room  tempera- 
ture" have  an  indefinite  value. 

An  additional  point  of  interest  is  that  in  certain  cases  the 
intensity  of  the  metabolism  remains  constant  throughout  the 
experiment,  notwithstanding  a  variation  in  the  temperature. 
This  is  shown  on  p.  152,  where  the  dog  was  given  320  grams  of 
meat.  The  amount  of  the  metabolism  scarcely  varied  with  the 
temperature.  The  chemical  regulation,  or  the  increased  heat 
production  brought  about  by  a  reduction  of  the  surrounding 
temperature,  is  not  evident  in  this  case.  Here  the  fuel  value  of 
the  food  was  equal  to  the  requirement  of  the  body  even  at  a 
temperature  of  7°. 

From  the  general  results  of  these  experiments  Rubner^ 
deduces  two  important  laws  which  govern  metabolism  as  in- 
fluenced by  temperature.  Their  significance  will  be  better  ap- 
preciated in  the  analysis  of  the  subject  in  the  following  chapter. 

"  The  first  law  is  that,  within  limits  normally  compatible  with 
life,  warm-blooded  animals  are  capable  of  adapting  themselves  to 
change  in  external  temperature  through  a  reflex  increase  or  de- 
crease of  the  activity  of  their  heat- producing  apparatus.  For 
every  state  of  body  substance  and  for  every  temperature  of  the 
environment  there  is  a  definite  amount  of  heat  loss  to  which  the 
organism — with  the  aid  of  its  heat-regulating  apparatus — tends 
to  approach.     This  may  be  called  the  minimal  heat  requirement. 

'  Rubner:  "Die  Gesetze  des  Energieverbrauchs,"  1902,  jj.  160. 


154  SCIENCE    OF   NUTRITION. 

There  is  no  law  enforced  with  greater  severity  or  fatality.  The 
starving  man  who  lives  on  his  own  substance  cannot  remove 
himself  from  its  influence.     Inexorable  until  the  last  hour  of  life 

it  demands  fulfilment It  kills  the  starving  child  in 

days,  while  it  allows  the  starving  adult  weeks." 

"The  second  law  concerning  the  relation  of  external  tem- 
perature to  the  organism  is:  The  mechanism  of  the  physical 
regulation  of  body  temperature  can  never  enter  as  a  factor  until 
the  heat  production  equals  the  requirement  of  the  organism.  If, 
however,  the  heat  production  he  greater  than  corresponds  to  the 
minimal  requirement  for  that  temperature,  then  the  heat  production 
within  certain  limits  becomes  independent  of  the  temperature. 
Under  these  circumstances  the  heat  production  does  not  decrease 
on  raising  the  external  temperature,  and  only  increases  when 
through  increasing  cold  the  former  heat  production  no  longer 
covers  the  minimal  requirement  of  the  organism  for  heat." 

This  second  law  explains  why  in  certain  cases  after  food 
ingestion  the  carbon  dioxid  excretion  may  remain  constant 
at  different  temperatures  of  environment.  Its  action  is  seen  in 
the  dog  mentioned  on  page  152,  after  he  had  eaten  320  grams  of 
meat  at  various  room  temperatures.  The  increase  in  body 
metabolism  due  to  the  stimulus  of  cold  (chemical  regulation) 
is  not  necessary,  since  heat  in  excess  of  the  requirement  is  already 
available.  All  that  is  needed  is  the  arrangement  of  avenues  of 
escape  for  the  excess  of  heat  produced  from  the  food  ingested 
(physical  regulation) .  This  physical  regulation  is  brought  about 
by  the  evaporation  of  water  and  by  a  change  in  the  distribution 
of  the  blood. 

How  the  increased  evaporation  of  water  enters  as  a  refrigerat- 
ing factor  is  beautifully  shown  in  the  experiment  on  the  dog 
(p.  152)  which  fasted  and  then  received  100,  200,  and  320 
grams  of  meat  at  various  room  temperatures.  The  distribution 
of  the  loss  of  heat  by  radiation  and  conduction  and  by  the 
evaporation  of  water  was  as  follows : 


THE   INFLUENCE   OF   PROTEIN   FOOD. 


^S5 


DISTRIBUTION    OF   HEAT    LOSS    FROM 

A    DOG  AFTER   ME.\T 

INGESTION. 

Hunger. 

100  Grams 

200  Grams 

320  Grams 

Meat. 

Meat. 

Meat. 

§   . 
•43  c 

L 

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a 

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c3 

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0 

u 

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78.5 

7-9 

67.1 

10.6 

78.5 

9-4 

15° 

55-3 

7.7  '  ... 

. .  . 

46.7 

11.2 

76.2 

10.4 

20° 

45-3 

10.6  1  46.7 

9.2 

49-5 

15-4 

. .  . 

. .  . 

25° 

41.0 

13.2      ... 

..  . 

. .  . 

..  . 

30° 

33-2 

23.0     34.1 

21-5 

27.8 

35-b 

34-5 

48-5 

It  is  evident  from  the  above  that  the  greater  part  of  the  loss 
of  heat  at  a  low  temperature  was  by  radiation  and  conduction, 
but  at  a  high  temperature  (30°)  the  loss  by  the  evaporation  of 
water  was  largely  increased.  The  extra  heat  production  on 
account  of  the  specific  dynamic  action  of  the  protein,  was  lost 
through  the  increased  evaporation  of  water. 

Much  meat  on  a  hot  day  would  therefore  seem  contraindi- 
cated. 

While  the  chemical  regulation  protects  the  body  from  an 
abnormal  fall  in  temperature,  the  physical  regulation  prevents 
an  abnormal  rise  in  temperature.  The  organism  may  be  at 
times  under  the  influence  of  one  means  of  regulation,  at  times  of 
the  other,  and  without  being  conscious  of  any  difference. 

Cold-blooded  animals  have  no  chemical  regulation,  and 
their  temperature  falls  with  that  of  their  surroundings. 

The  following  chapter  will  more  fully  discuss  the  cause  of 
the  specific  dynamic  action  of  the  foodstuffs. 


CHAPTER  VI. 
THE  SPECIFIC  DYNAMIC  ACTION  OF  THE  FOODSTUFFS. 

A  study  of  the  specific  dynamic  action  of  protein  in  its  re- 
lation to  temperature  changes  gave  Rubner^  new  points  of  view. 
He  saw  (experiment  on  p.  152)  that  by  chemical  regulation  the 
metabolism  in  a  fasting  dog  was  increased  from  54  to  86  calories 
per  kilogram,  an  increment  of  32.  And  he  likewise  observed 
that  after  the  ingestion  of  320  grams  of  meat  the  heat  pro- 
duced at  a  room  temperature  of  30°  rose  from  56  in  starvation 
to  83,  a  difference  of  27  calories.  The  source  of  the  increase 
through  chemical  regulation  is  known  to  be  chiefly  in  the 
muscles.  The  increase  brought  about  by  protein  ingestion  had 
been  shown  by  Rubner  to  be  due  not  to  any  such  thing  as 
intestinal  activity  (Darmarbeit),  but  rather  to  some  specific 
heat-raising  effect  of  protein  metabolism  itself.  It  was  apparent 
that  these  two  sources  of  increased  heat  might  enter  into  a 
reciprocal  arrangement  because  on  cooling  the  atmosphere  in 
which  the  dog  lived  to  7°  C,  the  metabolism,  after  the  ingestion 
of  320  grams  of  meat,  remained  at  87.9  calories  in  contrast  with 
83.0  on  feeding  at  30°.  Here  the  heat  due  to  the  specific  dy- 
namic action  was  used  in  replacement  of  that  induced  by 
chemical  regulation.  This  illustrates  Rubner's  modified  idea 
of  his  compensation  theory,  or  a  reciprocity  between  heat  pro- 
duced in  the  muscles  by  chemical  regulation  and  the  extra  heat 
production  brought  about  through  the  ingestion  of  food. 

Since  the  extra  heat  production  after  food  ingestion  could 
be  utilized  instead  of  heat  from  chemical  regulation,  Rubner 
perceived  that  the  true  increase  through  specific  dynamic  action 
could  be  measured  only  at  the  temperature  of  2)Z°i  where  there 
was  no  reflex  increase  in  metabolism  through  chemical  regula- 
tion. 

^  Rubner:   " Energiegesetze,"  p.  145. 
156 


SPECIFIC  DYNAMIC  ACTION   OF   FOODSTUFFS. 


157 


It  was  especially  important  to  make  experiments  regarding 
the  action  of  foodstuffs  at  a  temperature  of  33°,  for  that  is  the 
temperature  with  which  man  surrounds  his  skin.  By  means 
of  clothes  and  artificial  heating  man  constantly  tries  to  re- 
move himself  from  the  influence  of  chemical  regulation.  His 
daily  life  is  practically  under  the  influence  of  a  tropical  climate. 
His  metabolism  is  unchanged  from  the  normal  when  he  is  im- 
mersed in  a  bath  at  ^2^°} 

Rubner  therefore  planned  an  experiment  in  which  a  dog  was 
kept  at  a  temperature  of  ^7,°.  At  times  the  animal  was  made 
to  fast  in  order  that  the  basal  requirement  could  be  determined, 
and  during  other  definite  periods,  meat,  fat,  and  carbohydrates, 
either  alone  or  combined,  were  ingested,  and  the  increased 
metabolism  due  to  the  varying  dietaries  was  noticed.  The 
experiment  extended  over  a  period  of  forty-six  days. 

A  summary  of  the  results  obtained  is  shown  in  the  following 
table  and  is  graphically  illustrated  by  the  accompanying  figure 
9,  which  has  been  taken  from  Rubner.^ 


TABLE  INDICATING  THE  SPECIFIC  DYNAMIC  ACTION  OF  DIF- 
FERENT FOODSTUFFS  AT  33°. 
Values  in  Calories  per  Kilogram  Body  Weight. 


Diet-* 

Hunger 
Require- 
ment. 

Food  In- 
gested. 

Protein 
Ingested. 

Metab- 
olism. 

Increase 
above  Hun- 
ger IN  Per 
Cent. 

100  per  cent,  fat 

54-0 
53-5 
53-4 

52.5 

52.0 
SI.O 

51-0 
50.0 
50.0 
50.0 

53-4 
37-7 

55-5 

59-3 
63.0 

59-8 
60.3 
48.0 
43-6 
34.5 

32.3 

10.5 

57-1 
8.8 

56.3 
8.1 

31.6 

60.9 
62.1 

60.6 

63.6 

73-8 
55-6 
67.3 
52.0 

52.5 
60.4 

12.7 
16.0 

134 

2I-S 

41.9 

9.0 

31-9 
4.0 

S-o 
20.8 

66  per  cent,  meat 

10  per  cent,  meat \ 

90  per  cent,  fat / 

20  per  cent,  meat \ 

80  per  cent,  fat j 

100  per  cent,  meat 

Meat,  fat,  sugar 

100  per  cent,  meat 

Meat,  fat,  starch 

87  per  cent,  sugar 

66  per  cent,  meat 

*  percentages  are  in  terms  of  the  starvation  requirement  and  are  approximate  only. 

'Rubner:   "Archivfiir  Hygiene,"  1903,  Bd.  xlvi,  p.  390. 
'Rubner:   " Energiegesetzc,"  p.  324. 


158 


SCIENCE    OF    NUTRITION. 


It  is  clearly  evident  that  meat  ingestion  raises  the  metabo- 
lism most,  fat  next,  and  sugar  least  of  all  the  foodstuffs.  The 
ingestion  of  the  starvation  requirement  for  energy  in  the  form 
of  fat  raises  the  metabolism  12.7  per  cent.  During  the  two 
periods  when  approximately  100  per  cent,  of  the  basal  require- 
ment was  ingested  as  meat  there  was  an  average  increase  in 
the  metabolism  of  36.7  per  cent. 


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Fig.  9. — Rubner's  chart  indicating  the  specific  dynamic  action  of  different 
foodstuffs  ingested  at  a  room  temperature  of  33°.  The  dotted  line  indicates 
the  height  of  the  fasting  metabolism. 


More  detailed  examination,  however,  reveals  the  fact  that 
the  exact  quantity  of  meat  ingested  contained  119.6  per  cent, 
of  the  basal  requirement  of  calories,  of  which  iio.i  were  con- 
tained in  meat  protein  and  the  balance  in  fat  present  in  the  meat. 
If  under  the  influence  of  the  ingestion  of  119.6  per  cent,  of  the 
basal  requirement  the  metabolism  rose  36.7  per  cent.,  then  the 
increase  due  to  the  ingestion  of  100  per  cent,  would  have  been 


SPECIFIC   DYNAMIC    ACTION   OF    FOODSTUFFS.  1 59 

30.74  per  cent.  But  this  meat  containing  loo  per  cent,  of  the 
basal  requirement  in  reality  consisted  of  meat  protein  contain- 
ing 92.06  per  cent,  of  the  energ}'  and  of  fat  containing  the  re- 
maining 7.94  per  cent.  Since  the  ingestion  of  fat  sufficient  to 
provide  loo  per  cent,  of  the  basal  requirement  for  energy  raises 
metabolism  12.7  per  cent.,  then  fat  sufficient  to  provide  7.94 
per  cent,  of  the  basal  requirement  must  increase  metabolism 
7.94  X  0.127  or  1. 01  per  cent. 

Deducting  this  i.oi  per  cent,  which  is  due  to  the  specific 
d}-namic  action  of  the  fat  ingestion  from  the  total  increase  of 
30.74  per  cent.,  it  is  found  that  29.73  per  cent,  increase  is  due  to 
the  92.06  per  cent,  of  pure  meat  protein  ingested. 

If  92.06  per  cent,  of  meat  protein  raises  the  metabolism 
29.73  per  cent.,  then  100  per  cent,  of  such  protein  will  increase 
it  by  32.28  per  cent.  Using  the  same  procedure  in  computing 
the  heat-raising  power  of  two-thirds  the  basal  requirement  of 
energ)'  for  the  dog,  ingested  in  the  form  of  meat,  it  was  calcu- 
lated that  if  100  per  cent,  of  the  requirement  had  been  the 
quantity  supplied  the  increase  in  the  metabolism  would  have 
been  29.60  per  cent.     Rubner  therefore  found  that — 

I.  After  ingesting  meat  in  excess  of  the  starvation  metabo- 
lism, the  specific  dynamic  action  caused  a  heat  increase  of  32.28 
per  cent. 

II.  After  ingestion  of  a  quantity  smaller  than  that  of  the 
starvation  metabolism  the  specific  dynamic  action  similarly 
measured  was  29.60  per  cent. 

The  average  of  these,  or  30.94  per  cent.,  represents  the 
specific  dynamic  action  of  protein  or  the  increased  heat  pro- 
duction after  the  ingestion  of  meat  containing  100  per  cent,  of 
the  energy  requirement,  when  the  animal  is  outside  of  the 
influence  of  the  chemical  regulation. 

In  another  case,  after  the  ingestion  of  meat  in  large  excess, 
Rubner  finds  the  increase  due  to  the  specific  dynamic  action  to 
be  32.2  per  cent.     The  action  of  gelatin  is  similar,  the  increase 


l6o  SCIENCE   OF  NUTRITION. 

in  metabolism  being  28.0  per  cent,  for  every  100  calories  in 
the  gelatin  ingested. 

Again  Rubner^  has  determined  the  amount  of  the  metabolism 
of  a  fasting  dog  and  that  of  the  same  dog  made  diabetic  with 
phlorhizin  (see  p.  287).  Under  the  latter  circumstances  the 
protein  metabolism  is  greatly  increased.  He  found  that  for 
every  100  calories  increase  in  body  protein  broken  down  there 
was  an  increased  heat  production  of  31.9  calories.  Here  was  a 
rise  in  heat  production  not  due  to  protein  ingestion  and  there- 
fore not  due  to  intestinal  work,  but  due  to  the  mere  fact  of 
increased  protein  metabolism  in  starvation.  The  specific 
dynamic  action  of  protein  then  may  thus  be  tabulated : 

Increased  Heat  Production  for  every  ioo  Calories 
Ingested  or  Metabolized. 

Meat  protein 30.9 

Gelatin 28.0 

Body  protein  (phlorhizin  diabetes) 31.9 

It  has  furthermore  been  shown  by  Falta,  Grote,  and  Staehelin^ 
that  casein  and  the  amino-acids  resulting  from  the  hydrolysis 
of  casein  when  given  to  a  dog  exert  the  same  specific  d)aiamic 
action  as  do  the  proteins  of  meat. 

Regarding  cane  sugar,  the  experiment  shows  that  after  its 
ingestion  to  the  extent  of  providing  86.41  per  cent,  of  the  starva- 
tion requirement  for  energy,  the  metabolism  increased  only  5 
per  cent.  It  may  be  calculated  that  if  100  per  cent,  of  the  basal 
requirement  had  been  given  the  increase  would  have  been  5.8 
per  cent. 

Summarizing,  it  is  evident  that  if  the  same  quantity  of  energy 
be  contained  in  the  ingested  food  as  the  body  requires  in  starva- 
tion at  a  temperature  of  33°  C,  there  will  be  the  following 
increases  in  heat  production : 

Protein 30.9  per  cent. 

Fat 12.7  per  cent. 

Cane  sugar 5.8  per  cent. 

^  Rubner:   "Energiegesetze,"  p.  370. 

^  Falta,  Grote,  and  Staehelin:  "Hofmeister's  Beitrage,"  1907,  Bd.  ix,  p.  334. 


SPECIFIC    DYNAMIC   ACTION   OF    FOODSTUFFS.  l6l 

Food  equal  to  the  basal  requirement  of  energy  in  starvation 
at  the  temperature  of  33°  cannot  therefore  maintain  the  body 
in  calorific  equilibrium.  Rubner,  however,  calculates  the  fol- 
lowing as  the  minima  of  ingestion  for  the  three  foodstuffs,  when 
the  hunger  minimum  is  100: 

Hunger  minimum loo 

Protein  "        140.2 

Fat  "        II4-5 

Cane  sugar  minimum io6.^ 

In  other  words,  if  100  calories  be  the  starvation  requirement, 
140  calories  must  be  supplied  if  calorific  equilibrium  is  to  be 
maintained  by  the  ingestion  of  protein  alone ;  whereas  in  the  case 
of  sugar,  106.4  calories  are  all  that  are  required  to  prevent  the 
loss  of  energy  content  from  the  body's  material.  That  these 
results  are  not  limited  in  their  application  is  shown  by  Rubner' s^ 
experiment  on  a  man  who  was  given  1 20  per  cent,  of  the  starva- 
tion requirement  of  energy  first  in  the  form  of  sugar  and  then 
of  meat.     The  metabolism  was  as  follows: 

Starvation 2042  calories  in  24  hours. 

Sugar  alone 2087       "         "  "       " 

Meat  alone 2566       "         "  "       " 

As  neither  man  nor  dog  ever  lives  on  meat  alone  except  under 
forced  feeding,  the  results  are  not  usually  so  pronounced  as  in 
the  above  case.  Average  dietaries,  according  to  Rubner,'  show 
the  following  distribution  of  percentage  of  calories: 

PERCENTAGE  OF  CALORIES  IN  DIFFERENT  DIETS. 

Protein.  Fat.  Carbohydrates. 

I. — Well-to-do  individual 19.2  29.8  51.0 

II. — Workman 16.7  16.3  66.9 

III. — Exceptional  cases 8.3  38.7  52.8 

It  is  possible  to  calculate  the  specific  dynamic  effect  of  such 
diets  by  muhiplying  the  quantities  of  foodstuffs  by  their  specific 
dynamic  factor, — for  example,  loo  per  cent,  of  protein  =  30.9 
per  cent,  increase;    i  per  cent.  =  0.309  per  cent,  increase,  and 

'Rubner:   "  Energiegesetze,"  p.  410. 
'  Rubner:    Iliid.,  p.  415. 


1 62  SCIENCE    OF   NUTRITION. 

therefore  19.2  per  cent,  protein  in  the  food  must  cause  an  in- 
crease of  0.309  X  19.2  =  5.93  per  cent,  in  the  metabolism  due  to 
the  ingestion  of  protein  in  Diet  I. 

Calculating  the  diets  as  above,  the  following  figures  are 
obtained : 

L     Protein 19.2   X  0.309   =   5.93 

Fat 29.8  X  0.127   =  3.77 

Carbohydrate 51.0    X   0.058    =   2.96 

+   12.66  per  cent. 

II.     Protein 16.7   X  0.309   =   5.15 

Fat 16.3   X   0.127   =   2.06 

Carbohydrate 66.9   X  0.058   =  3. 88 

+   11.09  psr  cent. 

III.     Protein 8.3   X  0.309    =  2.56 

Fat 38.7   X   0.127   =  4.91 

Carbohydrate 52.8   X  0.058   =   3.06 

+    10.53  ps^  cent. 

Thus,  if  the  starvation  requirement  for  energy  be  ingested 
the  increase  in  metabolism  would  be : 

Diet     1 12.66  per  cent. 

"     II 11.09 

"   III 10.52 

and  from  this  it  may  be  calculated  that  calorific  equilibrium 
would  be  reached  by  ingesting  the  following  increases  above  the 
starvation  requirement: 

Diet     1 14.4  per  cent. 

"     II 12.4         " 

"   III II. I 

On  an  average  mixed  diet  the  ingestion  minimum  is  therefore 
between  ii.i  and  14.4  per  cent,  above  the  starvation  requirement. 
This  would  be  the  maintenance  requirement.     (Rubner.) 

Should  the  fasting  metabolism  of  a  man  be  2400  calories, 
the  ingestion  of  food  would  act  as  follows : 

Diet  I.  Diet  IIL 
(19.2%  protein)  (8.3%  protein) 
After    ingestion    of    starvation    require- 
ment of  energy 2703  2652 

After    ingestion    of    maintenance    min- 
imum  2745  2666 


SPECIFIC   DYNAMIC   ACTION   OF   FOODSTUFFS.  1 63 

That  mixtures  of  .the  foodstuffs  do  act  nearly  after  this 
fashion  Rubner  has  proved. 

On  account  of  the  great  specific  d}-namic  action  of  protein, 
Rubner  would  restrict  its  use  in  fever  and  substitute  carbohy- 
drates as  the  source  of  energy. 

During  the  heated  term  of  midsummer,  diminution  of 
protein  ingestion  will  materially  improve  the  personal  comfort 
by  decreasing  the  heat  production  and  the  consequent  necessity 
for  sweat  production  (p.  217). 

As  to  the  cause  of  the  specific  dynamic  action,  Rubner  offers 
this  theory:  The  cells  of  an  organism  require  a  fixed  quantity 
of  potential  energy  which  must  be  furnished  to  them  in  metabol- 
izable  compounds.  This  quantity  is  the  same  for  all  tempera- 
tures and  free  heat  cannot  be  employed  for  this  purpose.  The 
value  of  the  foodstuffs  depends  upon  the  potential  energ}^  they 
can  give  to  the  cells.  If  cane  sugar  is  ingested,  for  example, 
3.1  per  cent,  of  its  energy  is  dissipated  as  heat  when  it  is  inverted 
into  levulose  and  dextrose.  This  heat  cannot  be  used  for  the 
life  processes  in  the  cells.  When  protein  breaks  up  in  metabo- 
lism, large  quantities  of  sugar  are  produced.  According  to 
Rubner,  this  earlier  metabolism  of  protein  yields  heat,  but  not 
energy  for  the  cells.  He  thinks  that  the  protein  sugar  and 
possibly  other  cleavage  compounds  may  in  this  case  be  the  true 
source  of  power  for  the  living  mechanism.  The  extra  heat  of 
the  earlier  process  which  is  wasted  when  the  environment  has 
a  temperature  of  33°,  may  however  be  used  as  a  substitute  in 
the  place  of  the  heat  which  may  be  required  by  chemical  regu- 
lation. Here  heat  and  not  potential  energy  is  required.  Bear- 
ing these  considerations  in  mind,  foodstuffs  are  replaceable  in 
accordance  with  their  respective  energy  equivalents. 

The  theory  may  be  schematically  indicated  as  follows: 

Starvation  Requirement  of  Potential  Energy  by  Cells  =  loo  Calories. 
140  Calories  in  Protein  of  Meat  Ingested. 

40  Calories  =  free  heat  liber-  100  Calories  =  Potential  en- 

ated  in  early  cleavage,  avail-  f^gy  from  protein  available 

able  in  rc[)lacement  of  heat  for  cell  life. 
of  chemical  regulation. 


164  SCIENCE    OF   NUTRITION. 

From  this  it  may  be  calculated  that  when  protein  is  metabol- 
ized 71.4  per  cent,  of  its  energy  content  is  available  for  cell  life, 
while  28.6  per  cent,  is  liberated  as  free  heat.  It  has  been  already 
shown  that  52.5  per  cent,  of  the  energ}^  contained  in  meat  protein 
may  be  liberated  in  dextrose  in  the  organism  (see  p.  132),  and 
this  may  be  directly  used  by  the  cells.  The  balance  of  the  71.4 
per  cent,  of  the  directly  available  energ}'  (=  a  residual  19  per 
cent.)  is  furnished  by  unknown  compounds.  As  regards  the 
source  of  the  free  heat  nothing  can  be  said  with  certaint}\  (See 
p.  361.) 


CHAPTER  VII. 

THE  INFLUENCE  OF  THE  INGESTION  OF  FAT  AND 
CARBOHYDRATES. 

In  a  previous  chapter  it  was  showii  that  the  amount  of  fat 
in  the  fasting  organism  materially  affected  the  amount  of  protein 
burned.  Where  there  was  much  fat  present  little  protein  was 
consumed;  where  there  was  little  fat,  much  protein  burned; 
and  where  there  was  no  fat,  protein  alone  yielded  the  energy 
necessary  for  life. 

The  ingestion  of  fat  alone  will  not  prevent  the  death  of  the 
organism  because  there  is  a  continual  loss  of  tissue  protein  from 
the  body,  which  finally  weakens  some  vital  organ  to  such  an 
extent  that  death  takes  place. 

In  a  fasting  animal  which  still  contained  fat,  Voit^  found  that 
the  ingestion  of  loo,  200,  and  300  grams  of  fat  scarcely  influenced 
the  protein  metabolism.  The  latter  was  slightly  increased,  if 
anything.     Voit's  table  is  as  follows: 

Fat.                Urea.  Fat.              Urea. 

o 1 1.9         300 12.0 

o 12.0  o 1 1.9 

100 12.0  o 1 1.3 

200 12.4 

To  another  dog,  which  in  starvation  burned  96  grams  of  fat, 
100  grams  were  given,  with  the  result  that  he  then  burned  97 
grams.  The  conditions  of  the  metabolism  in  both  cases  were 
therefore  identical.  The  fat  ingested  simply  burned  instead  of 
the  body's  fat,  but  the  total  amount  of  protein  and  fat  burned 
remained  the  same. 

One  reason  why  the  ingestion  of  fat  uj)  to  the  requirement 

'  Voit:   "Physiologic  des  Stoffwechsels  und  dtr  Krnahrung,"  1881,  p.  128. 

165 


1 66  SCIENCE   OF  NUTRITION. 

does  not  alter  the  metabolism  may  be  found  in  the  observation 
of  Schulz^  that  in  starvation  there  is  an  increase  in  the  quantity 
of  fat  in  the  blood,  and  of  Rosenfeld^  that  the  amount  of  fat  in 
the  liver  increases.  He  finds  that  a  fasting  liver  contains  lo  per 
cent,  of  fat.  If  carbohydrates  or  protein  (which  yields  car- 
bohydrate in  metabolism)  be  ingested,  the  fat  content  falls  to 
6.2  per  cent.  If  fat  be  given  to  a  fasting  dog,  the  liver  m^y 
contain  25  per  cent,  of  fat;  but  if  carbohydrates  are  ingested  at 
the  same  time,  the  liver  does  not  retain  the  fat,  which  must  be 
deposited  elsewhere.  Thus,  in  the  liver  there  is  an  antagonism 
between  glycogen  deposit,  which  follows  carbohydrate  ingestion, 
and  fat  deposition. 

Pfliiger^  gave  a  dog  fat  alone  in  large  quantities  for  thirty 
days  and  found  that  the  fresh  substance  of  the  liver  at  the  end 
of  the  period  contained  45  per  cent,  of  fat  and  no  glycogen. 

Miescher  found  fat  globules  in  the  muscle  cells  of  salmon 
after  their  five  to  fifteen  months'  fast  in  fresh  water,  during 
which  time  they  had  laid  their  eggs.  It  is  undoubted  that  the 
deposits  of  fat  in  the  adipose  tissue  of  these  fishes  are  drawn  on 
in  starvation,  and  that  the  blood  then  carries  to  the  hungry  cells 
aU  the  fat  they  require  for  their  continued  function.  It  seems 
that  the  fat  supply  to  the  ceUs  is  regulated  by  the  quantity  of 
other  foods  available,  and  that  even  in  starvation  there  is  at 
first  ample  fat  to  meet  the  requirement  of  the  organism.  These 
are  important  principles  which  will  be  further  discussed  when  the 
subject  of  fatty  infiltration  is  considered.  (See  chapter  on 
Diabetes.)  , 

As  explained  in  Chapter  VI,  the  small  increase  in  metabo- 
lism after  the  ingestion  of  fat  above  the  requirement  has  led 
Rubner*  to  determine  accurately  its  specific  dynamic  action. 
The  metabolism  does  not  rise  so  greatly  after  the  ingestion  of 

^  Schulz:   "Pflijger's  Archiv,"  1896,  Bd.  Ixv,  p.  299. 
^  Rosenfeld:   "Ergebnisse  der  Physiologie,"  1903,  Bd.  ii,  I,  p.  86. 
^Pfliiger:   "Pfliiger's  Archiv,"  1907,  Bd.  cix,  p.  123. 
*Rubner:   " Energiegesetze,"  1902,  p.  353. 


INGESTION  OF   FAT  AND   CARBOHYDRATES.  167 

fat  as  it  does  on  a  protein  diet.  If  the  hunger  minimum  of 
calories  at  33°  be  100,  then  114.5  calories  must  be  ingested  in 
fat  if  a  maintenance  diet  is  to  be  given.  This  energy  requirement 
is  140.2  in  the  case  of  protein  diet.  Protein  therefore  causes  a 
much  higher  heat  production  than  does  fat.  The  influence  of 
external  temperature  on  the  heat  production  after  ingesting  fat 
above  the  requirement  is  similar  to  that  after  meat  ingestion, 
only  not  so  pronounced.  Rubner^  gives  the  following  table, 
showing  the  effect  of  the  ingestion  of  171. 3  calories  in  fat 
per  kilogram  of  dog: 

SPECIFIC  DYNAMIC  ACTION  OF  FAT. 
171. 3  calories  in  fat  per  kg.  dog  were  ingested. 
Calories  per   Kilo. 
Temperature.  Starvation.     After  Fat  Ingestion.  Increase. 

2.7° 152. 1  155-5  +   2.2  per  cent. 

15-5° 83.1  93.4  +12.4       " 

31-0° 64.5  79.9  +23.9       " 

At  2.7°  the  excess  ingested  above  the  requirement  amounted 
to  12.6  per  cent.,  and  the  increase  in  heat  production  was  2.2 
per  cent. 

At  31°  the  excess  of  food  calories  above  the  requirement  was 
165  per  cent,  and  the  increase  in  heat  production  was  23.9  per 
cent.  In  this  instance  100  per  cent,  of  the  requirement  may  be 
calculated  to  raise  the  metabolism  14.4  per  cent,  at  a  tempera- 
ture of  31°.  This  represents  the  specific  dynamic  effect  of  fat 
on  the  metabolism.  As  in  the  cases  of  the  other  foodstuffs, 
this  action  is  to  be  explained  by  a  production  of  heat  in  early 
cleavage  processes  which  is  not  directly  available  for  the  cells 
of  the  organism. 

It  has  already  been  demonstrated  that  less  protein  is  burned 
in  starvation  when  the  body  is  fat  than  when  it  is  lean.  It 
would  therefore  seem  that  if  protein  and  fat  were  ingested  to- 
gether, a  similar  reduction  in  the  amount  of  the  protein  require- 
ment would  be  effected  (Voit). 

'Rubncr:    "Energiegesctzc,"  1902,  p.  119. 


i68 


SCIENCE    OF   NUTRITION. 


It  has  been  shown  in  a  previous  chapter  that  nitrogenous 
equihbrium  can  be  maintained  in  a  dog  only  after  the  ingestion 
of  three  and  a  half  times  the  quantity  of  protein  destroyed  in 
starvation.     (See  p.  109.) 

E.  Voit  and  Korkunoff/  continuing  these  experiments,  find 
that  if  fat  and  meat  be  ingested  together,  the  quantity  of  the 
latter  necessary  to  establish  nitrogenous  equilibrium  is  reduced 
to  between  1.6  to  2.1  times  the  starvation  minimum.  Much 
less  protein  food  is  therefore  required  to  maintain  the  body's 
protein  when  it  is  ingested  with  fat  than  when  it  is  given  alone. 
In  consequence  of  this,  protein"  is  more  readily  added  to  the 
body  when  fat  is  ingested  with  it,  as  is  seen  in  the  following  ex- 
periment of  Rubner^  on  a  man. 


INFLUENCE  OF  FAT  INGESTION  ON  NITROGEN  RETENTION. 


Food. 

N.  Metabolism. 

N. 

Fat. 

Carbohydrates. 

N  IN  Excreta. 

N  to  Body. 

23.6 

23-5 
23.0 

23-4 

99. 

195- 
214. 

35°- 

260 
226 
221 
234 

26.36 

21-55 

18.5 

17.6 

—3-64 
+  1.81 

+  4-13 
+  5-75 

With  increasing  quantities  of  fat  there  is  an  increasing 
addition  of  protein  to  the  body. 

It  has  already  been  shown  that  protein  ingested  alone  in 
large  quantity  establishes  nitrogen  equilibrium  at  a  higher  level, 
constantly  raising  the  amount  of  heat  produced  until  nitrogenous 
equilibrium  is  reached  (the  secondary  dynamic  rise,  p.  151). 

The  same  destruction  of  the  easily  oxidized  protein  takes 
place  when  it  is  given  with  fat,  as  was  shown  by  Voit^  in  the 
following  experiment  oil  a  dog: 

^  Voit  and  Korkunoff:    " Zeitschrif t  fiir  Biologic,"  1895,  Bd.  xxxii,  p.  117. 
^Rubner:  Von  Leyden's  "Handbuch  der  Erniihrungstherapie,"  1903,  Bd. 
i.  P-  43- 

^  Voit:  Hermann's  Handbuch,  "Physiologic  des  Stoffwechsels,"  1881,  p.  131. 


INGESTION   OF    FAT   AND   CARBOHYDRATES.  169 

THE    "SECONDARY    RISE"    IN    PROTEIN    METABOLISM    ON    A 


MEAT-FAT 

DIET. 

(Weights 

in  grams.) 

Food. 

Meat. 

Fat. 

Urea. 

Flesh  to  Body. 

1800 

0 

127.9 

26 

1800 

0 

127.6 

26 

1800 

250 

117.Q 

162 

1800 
1800 

250 
250 

II3-5 
120.7 

|i7i 

1800 

250 

II5-7 

J  164 

1800 

250 

119.7 

1800 
1800 

250 
250 

127-5 
130.0 

}" 

A  prolonged  deposition  of  protein  in  the  normal  adult,  even 
when  fat  is  given  with  it,  is  demonstrably  difficult. 

The  question  arises,  does  the  ingestion  of  large  quantities  of 
fat  also  cause  an  increase  in  the  metabolism  until  fat  combustion 
is  balanced  by  its  ingestion  ? 

Rubner^  has  shown  that  this  is  not  the  case.  He  cites  the 
record  of  the  following  long  respiration  experiment  on  a  dog 
which  w^as  given  80  grams  of  meat  and  30  grams  of  fat  daily: 

ABSENCE  OF  THE  "  SECONDARY  DYNAMIC  RISE  "  IN  FAT  METAB- 
OLISM ON  A  MEAT-FAT  DIET. 

(Fat  being  given  in  excess  of  the  requirement.) 

Calories  of  Met.abolism. 

Protein.  Fat.  Tot.\l. 


97.2 

173-0 

270.0 

83.0 

178.0 

261. 1 

89-3 

173-5 

262.7 

85.6 

163.2 

248.9 

87.8 

169.0 

256.8 

83.0 

159.6 

242.6 

74-4 

171. 7 

246.2 

78.0 

178.4 

256.3 

80.0 

179.6 

259-7 

The  diet  was  58.7  per  cent,  above  the  starvation  requirement. 
It  contained  354  calories,  of  which  21.5  per  cent,  were  in  protein. 
The  mean  heat  production  during  the  period  of  ingestion  of 
food  was  256.0  calories,  and  in  the  following  starvation  days 
223.2  calories,  .showing  an  increase  in  metabolism  of  11.2  per 
cent,  caused  by  an  excess  in  food  of  58.7  ])er  cent.     During 

'  Rubncr:   "Encrgicgesctzc,"  1902,  p.  251. 


lyo  SCIENCE   OF   NUTRITION. 

the  later  days  the  animal  was  in  nitrogenous  equilibrium. 
Notwithstanding  an  excess  of  fat  in  the  diet,  and  a  continued 
deposit  of  fat  in  the  body,  there  was  no  increase  in  the  metabolism 
during  the  time  of  experimentation.  The  secondary  dynamic 
action  noted  by  Rubner  as  regards  protein  does  not  therefore 
take  place  as  regards  fat.  The  storage  of  fat  in  the  body  is 
consequently  a  matter  of  comparative  ease, 

Rubner^  has  compared  the  metabolism  of  a  boy  who  was 
obese  with  that  of  his  brother,  who  was  a  year  older,  but  thin. 
They  were  the  children  of  parents  of  small  means  and  would 
not  naturally  be  overfed.  The  interesting  point  of  the  experi- 
ment was  whether  obesity  was  due  to  a  reduced  metabolism 
with  the  consequent  deposition  of  fat.  Each  boy  was  given  a 
maintenance  diet,  or  one  which  balanced  his  metabolism,  with- 
out adding  to  or  subtracting  from  his  body  substance.  The 
general  results  are  as  follows : 

Fat  Boy.  Thin  Boy. 

Age  in  years lo  ii 

Weight  in  kilograms 41  26 

Total  calories  of  metabolism 1 786.1  i3S2-i 

Calories  per  kilogram 43.6  52.0 

Calories  per  sq.  m.  surface 1321.  1290. 

The  comparison  shows  that  the  fat  brother  had  a  larger  total 
metabolism  than  the  thin  one,  but  the  fat  boy  also  had  the 
larger  surface.  Per  square  meter  of  surface  the  metabolism 
was  the  same.  The  gradual  increase  in  the  area  of  the  body 
caused  by  filling  out  the  fat  cells  may  therefore  increase  com- 
bustion, but  this  is  not  due  to  the  specific  action  of  the  fat  on 
metabolism  as  in  the  case  of  the  secondary  dynamic  rise  after 
protein  ingestion,  but  rather  to  the  increase  in  the  size  of  the 
body.  Carbohydrates,  which  in  excess  are  converted  into  fat, 
must  behave  in  the  same  way. 

It  will  be  noticed  that  in  the  experiment  where  80  grams  of 
meat  and  30  grams  of  fat  were  daily  ingested,  although  the  pro- 
tein metabolism  gradually  fell,  the  fat  metabolism  gradually 

^Rubner:   " Beitrage  zur  Ernahrung  im  Knabenalter,"  1902. 


INGESTION  OF  FAT  AND   CARBOHYDRATES.  171 

rose,  and  in  isodynamic  relation  to  the  fall  in  protein.  Allowing 
for  the  difference  in  specific  dynamic  action  protein  and  fat 
replace  each  other  in  metabolism  in  isodynamic  quantities. 

Up  to  the  present  the  discussion  of  metabolism  has  been  con- 
fined to  the  combustion  of  protein  and  fat  in  starvation  and  after 
their  ingestion.  There  is,  however,  another  great  class  of  food- 
stuffs w'hich  in  man  play  a  predominant  part  in  nutrition, — the 
carbohydrates. 

Starch,  milk  sugar,  and  cane  sugar  are  all  converted  into 
monosaccharids  in  the  intestinal  tract,  and  dextrose,  galactose, 
and  levulose,  formed  from  them,  have  similar  physiological 
value  in  the  cells.  All  three  are  glycogen  formers,  and  thus 
galactose  and  le\ailose  may  be  partly  converted  into  dextrose 
through  the  glycogen  stage. 

It  has  already  been  noted  that  starvation  greatly  reduces  the 
quantity  of  glycogen  in  the  animal  body.  If  under  these  cir- 
cumstances dextrose,  levulose,  or  galactose  be  ingested  in  con- 
siderable quantity  and  the  animal  be  killed  eight  hours  after  the 
experiment,  large  quantities  of  glycogen  are  found  stored  in 
the  liver  and  muscles.  The  amount  in  the  liver  may  be  as  high 
as  forty  per  cent,  of  the  dry  solids  of  that  organ. ^  The  quantity 
found  is  much  more  than  could  have  originated  from  the  pro- 
tein metabolism  of  the  time.  There  is  therefore  no  doubt  that 
these  sugars  are  directly  converted  into  glycogen  through 
dehydration. 

The  quantity  of  glycogen  present  in  a  living  animal  cannot 
be  accurately  estimated.  Schondorf^  gave  seven  dogs  rich 
carbohydrate  diets  for  several  days  and  found  that  the  quantity 
of  glycogen  present  in  their  bodies  varied  between  7.59  and  37.87 
grams  per  kilogram. 

The  distribution  of  this  glycogen  in  too  grams  of  the  fresh 
tissue  varied  as  follows : 

'  Voit:  "Zeitschrift  fiir  Biologic,"  1891,  Bd.  xxviii,  p.  245. 
*Schondorf:   "Pflugcr's  Archiv,"  1903,  Bd.  xcix,  p.  191. 


172  SCIENCE    OF   NUTRITION. 

Maximum.  Minimum. 

Liver 18.69  7-3 

Muscle 3.72  0.72 

Heart 1.32  0.104 

Bone 1.90  0-I97 

Intestines 1.84  0.026 

Skin 1.68  0.09 

Brain 0.29  0.047 

Blood 0.0066  0.0016 

The  traditional  distribution  of  glycogen,  one-half  to  the  liver 
and  one-half  to  the  rest  of  the  body,  Schondorf  shows  to  be  in- 
correct. For  100  grams  of  liver  glycogen  there  occurred  in  the 
rest  of  the  body  the  following  amounts: 

Dog       1 398  grams. 

II 279 

III 87 

IV 76 

V 159 

VI 355 

VII 105 

It  is  an  interesting  observation  of  Kiilz^  and  of  Jensen^  that 
an  active  organ  like  the  heart  maintains  its  normal  glycogen 
content  even  after  fifteen  days  of  starvation. 

In  the  various  discussions  on  the  subject  of  glycogen  it  has 
been  shown  that  in  starvation,  and  after  protein  and  sugar  in- 
gestion, there  is  glycogen  present  in  the  body, — a  constant 
supply  always  ready  for  emergencies,  which  can  be  reduced 
through  exercise  but  which  is  only  to  be  completely  removed 
by  tetanic  convulsions  (pp.  79  and  281). 

The  writer  has  here  avoided  the  discussion  of  a  production 
of  sugar  from  fat.  To  his  mind  the  evidence  is  against  such 
production,  as  will  be  demonstrated  in  the  chapter  on  Diabetes. 

If  carbohydrates  be  ingested  alone  immediately  after  star- 
vation the  protein  metabolism  may  fall  below  the  starvation 
amount.  This  appears  in  the  experiments  of  Voit,^  who  gave 
a  fasting  dog  500  grams  and  noticed  a  fall  in  protein  metabolism 
from  181  to  170  grams. 

^Kiilz:   "Festschrift  zu  Ludwig,"  1891,  p.  109. 

^Jensen:   "Zeitschrift  fiir  physiologische  Chemie,"  1902,  Bd.  xxxv,  p.  525. 

^Voit:   Hermann's  Handbuch,  "Stoffwechsel,"  1881,  p.  140. 


INGESTION   OF   FAT   AND    CARBOHYDRATES. 


73 


Rubner^  was  able  to  reduce  the  nitrogen  in  the  urine  of  a 
man  from  11.9  to  6.3  grams,  or  nearly  one-half,  by  causing  the 
subject  to  ingest  a  diet  rich  in  carbohydrates. 

This  higher  protein-sparing  property  gives  to  dogs  fed  on 
carbohydrates  alone  a  longer  lease  of  life  than  is  granted  to  those 
fed  on  fat  alone,  although  the  ultimate  outcome  is  the  same. 

The  effect  of  feeding  with  easily  absorbable  sugar  in  excess 
is  shown  in  the  following  experiment  of  Rubner^  on  a  dog: 

INFLUENCE  OF  CANE  SUGAR  ON  THE  METABOLISM  OF  A  DOG. 


Food. 

N  IN  Ex- 
creta IN 
Grams. 

C  Retained 
from  Carbo- 
hydrates IN 
Grams. 

Cal. 

FROM 

Protein. 

Cal.  from 
Fat  OR  Car- 
bohydrates. 

Calories, 
Total. 

Starvation 

1.92 
1.82 
0.91 
0.72 
0.56 

0-53 
0.69 

10.18 

17.81 

17.61 

6.70 

48.0 

45-5 
22.7 
18.0 
14.0 
13.2 
17.2 

203.4 
208.0 
224.4 

245-9 

247.7 

208.8 

251-4 

253-0 
247.1 

263.9 
261.7 

226.0 

Starvation 

85  grams  cane  sugar  . . 
no     "           "       " 
no     "           "       " 
120     "           "       " 
Starvation 

The  protein  metabolism  may  thus  be  reduced  to  one-third 
the  fasting  value,  a  result  also  obtained  by  Landergren^  and 
byFolin^  in  man.  Cathcart^  gave  a  man  who  had  been  fasting 
fourteen  days  a  diet  of  cream  (300  c.c.)  and  starch  (400  grams). 
The  nitrogen  excretion  in  the  urine  was  as  follows: 

Total  N.  Urea  N. 

Day  14  of  starvation 7.78  5.99 

"      I  on  cream-starch  diet 7.43  5.80 

"     2  "       "  "         "   3.58  2.29 

"     3  "       "  "         "   2.84  1.76 

The  absence  of  a  fall  in  protein  metabolism  on  the  first  day  is 
probably  to  be  explained  by  assuming  a  large  deposit  of  glycogen 

'Rubner:   von  Leyden's  Handbuch,  1903,  vol.  i,  p.  44. 
'Rubner:   "Die  Gesclze  des  Energicverbrauchs,"  1902,  p.  341. 
'Landcrgren:   ".Si<an.  Archiv  fiir  Physiologic,"  1903,  Bd.  xiv,  p.  112. 
*Koiin:   "American  Journal  of  Physiology,"  1905,  vol.  xiii,  p.  45. 
'Calhcart:   "Biochemische  Zeitschrift,"  1907,  Bfl.  vi,  p.  109. 


174 


SCIENCE    OF   NUTRITION. 


within  the  body  at  the  expense  of  the  starch  ingested  (see  p.  147). 
On  the  third  day  of  the  diet  the  protein  metabolism  had  fallen 
to  one-third  that  observed  in  fasting. 

The  quantity  of  sugar  utilized  by  Rubner's  dog  above 
mentioned  was  35.7  to  80.6  per  cent,  above  the  starvation  re- 
quirement for  energy  (the  cane  sugar  eliminated  in  the  urine 
was  deducted  from  that  ingested,  in  order  to  determine  the  quan- 
tity utilized).  The  experiment  was  done  at  33°,  and  the  specific 
dynamic  action  of  the  cane  sugar  may  be  calculated  as  raising 
the  metabolism  5.36  per  cent,  on  an  average. 

The  experiment  also  illustrates  the  ready  retention  of  car- 
bohydrate carbon  in  the  body.  It  is  well  loiown  that  such  carbon 
may  be  stored  in  the  body  as  glycogen,  but  its  retention  often 
exceeds  the  animal's  ability  to  hold  glycogen. 

Voit,  when  he  wrote  his  "Physiologic  des  gesammt  Stoff- 
wechsels  und  der  Ernahrung,"  in  1881,  was  unable  to  give 
definite  proofs  of  the  conversion  of  carbohydrate  into  fat  in 
the  organism,  although  such  conversion  was  popularly  believed 
to  take  place. 

Definite  proof  of  the  conversion  of  carbohydrates  into  fat 
was  afforded  by  Meissl  and  Strohmer,^  who  gave  a  pig,  weighing 
140  kilos,  two  kilograms  of  rice  containing  1592  grams  of  starch 
daily  for  seven  days,  and  collected  the  carbon  and  nitrogen  of  the 
excreta  by  means  of  a  Pettenkofer-Voit  apparatus  during  two 
days  of  the  period.    The  average  results  per  day  were  as  follows : 

Carbon.  Nitrogen. 

Ingested  in  food 765.37  18.67 

Excreted 476.15  12.59 

Balance  retained  in  the  body 289.22  6.08 

The  nitrogen  retained  represented  38  grams  of  protein  con- 
taining 20.1  grams  of  carbon;  269.12  grams  of  retained  carbon 
were  therefore  available  for  glycogen  or  fat  construction.  Since 
the  amount  of  carbon  retained  exceeded  the  possible  glycogen 

^Meissl  and  Strohmer:  " Sitzungsberichte  der  k.  Acad.  d.  Wissenschaften," 
1883,  Bd.  Ixxxviii,  III  Abtheilung. 


INGESTION  OF   FAT   AND   CARBOHYDRATES.  1 75 

formation,  fat  must  therefore  have  been  added  to  the  body. 
Had  all  the  carbon  retained  been  converted  into  fat  it  would 
represent  a  production  of  343.9  grams  of  fat.  Of  this  only  33.6 
grams  of  fat  could  have  arisen  from  the  protein  metabolism  of 
the  period.  Hence  it  is  possible  that  310.3  grams  of  fat  may  have 
originated  from  1592  grams  of  starch  ingested,  which  indicates 
a  conversion  of  19.5  per  cent,  of  the  starch  given  into  fat. 

Similar  experiments  were  made  with  geese  by  E,  Voit  and 
C.  Lehmann.^  The  geese  were  starved  four  and  a  half  days 
and  were  then  fed  with  rice. 

Pne  of  these  respiration  experiments  which  lasted  thirteen 
days  has  recently  been  published^  and  is  as  follows : 

Nitrogen.  Carbon. 

In  the  2609  grams  of  rice 41-47  ii59-7 

In  the  excreta — 

Urine  and  feces 45-39  134-8 

Respiration ' 657.8 

.Total 45.39  792.4 

Change  in  the  body — 3.92  +367-3 

At  the  commencement  of  the  experiment  the  animal  weighed 
4  kilograms.  There  was  no  protein  retention,  but  31  per  cent, 
of  the  carbon  ingested  was  not  eliminated.  The  protein  metab- 
olism could  not  nearly  yield  enough  carbon  to  account  for  that 
retained.  As  the  rice  contained  but  0.51  per  cent,  of  ether  ex- 
tract the  retained  carbon  could  not  have  been  administered  in 
the  form  of  fat.  If  367.3  grams  of  carbon  had  been  retained  in 
the  form  of  glycogen  this  would  have  aggregated  851  grams,  or 
twenty  per  cent,  of  the  whole  goose.  This  is  a  manifest  impossi- 
bility, since  E.  Voit^  found  only  2.2  per  cent,  of  glycogen  in  a 
goose  which  had  been  largely  fed  on  rice.  Since  the  carbon 
retained  could  not  have  been  stored  as  glycogen,  the  only 
alternative  remaining  is  to  assume  its  retention  as  fat. 

Rubner  at  the  same  time  showed  the  same  principles  to  be 
true  in  the  case  of  the  dog. 

*  Voit:  "Sitzungsberichteder  kgl.  bayr.  Acad.  d.  Wisscnschaft,"  1885,  p.  288. 
'Lehmann  and  E.  Voit:   "Zeitschrift  fiir  Uiologie,"  1901,  Bd.  .xlii,  ]>.  644. 
'E.  Voit:   "Zeitschrift  fiir  Biologic,"  1888,  Bd.  xxv,  p.  543. 


1^6  SCIENCE   OF   NUTRITION. 

It  is  evident,  then,  that  pigs,  geese,  and  dogs  can  convert  car- 
bohydrates into  fat.  The  fattening  of  cattle  may  be  similarly 
accomplished. 

The  ability  to  convert  carbohydrate  into  fat  probably  exists 
throughout  the  animal  kingdom.  Thus  Weinland^  has  ex- 
pressed from  living  ascaris  ferments  which  convert  glycogen  into 
dextrose  and  then  into  valerianic  and  possibly  caproic  acids, — 
0.8  gram  of  dextrose  yields  0.3  gram  of  valerianic  acid.  (See 
p.  310.) 

This  is  suggestive  of  a  wide-spread  biological  capability. 

When  carbohydrates  are  converted  into  fat  in  the  organism 
the  respiratory  quotient  (^^J^^,  see  p.  28)  may  rise  very 
considerably  above  unity.  This  is  for  the  reason  that  an 
oxygen  rich  substance  like  dextrose  is  being  converted  into 
substance  which  is  poor  in  oxygen.  This  intramolecular 
oxygen  derived  from  dextrose  becomes  available  for  carbon 
dioxid  production  and  the  requirement  for  inspired  oxygen 
diminishes.  Hence  the  volume  of  expired  carbon  dioxid  may 
be  greater  than  the  volume  of  inspired  oxygen.  Max  Bleibtreu^ 
found  that  the  respiratory  quotient  of  a  goose  which  had  been 
stuffed  with  grain  was  1.33,  whereas  the  same  goose  when 
fasting  showed  a  normal  quotient  for  that  condition  of  0.728. 
Pembrey^  describes  how  marmots  previous  to  the  winter  hiber- 
nation instinctively  devour  large  quantities  of  carbohydrate  food, 
and  how  the  respiratory  quotient  may  rise  even  as  high  as  1.39. 
This  indicates  a  fat  production  for  use  during  the  winter. 

Johansson,  Billstrom,  and  Heijl*  have  shown  that  if  50  to  200 
grams  of  cane  sugar  be  given  a  fasting  man,  the  carbon  dioxid 
output  increases  from  22.6  grams  per  hour  to  about  30  grams 
per  hour.  The  larger  ingestion  does  not  produce  a  higher 
elimination  of  carbon  dioxid  than  does  the  smaller  amount. 

^  Weinland:  "Zeitschrift  fur  Biologie,"  1901,  Bd.  xlii,  p.  55;  Bd.  xliii,  p.  86; 
1903,  Bd.  xlv,  p.  113. 

^Bleibtreu:   "Pfliiger's  Archiv,"  1901,  Bd.  Ixxxv,  p.  345. 

^Pembrey:   "Journal  of  Physiology,"  1901,  vol.  xxvii,  p.  407. 

_  ''Johansson,  Billstrom,  and  Heijl:  "Skan.  Archiv  fiir  Physiologic,"  1904,  Bd. 
xvi,  p.  263. 


INGESTION   OF   FAT   AND    CARBOHYDRATES.  1 77 

This  indicates  the  evenness  with  which  sugar  entering  the  blood- 
stream is  utilized  by  the  organism.  If  sugar  be  present  in 
excess  it  may  be  stored  as  glycogen  until  it  is  needed  by  the  cells. 
The  increased  carbon  dioxid  output  does  not  mean  increased 
metabolism  in  the  sense  of  increased  heat  production,  but  the 
increase  due  to  the  destruction  of  carbohydrates  instead  of  fat 
in  the  production  of  the  same  amount  of  heat.  The  rise  in  the 
carbon  dioxid  output  is  greater  after  levulose  is  ingested  than 
after  dextrose  is  given.  This  is  explained  as  due  to  the  fact  that 
levulose  is  less  readily  retained  in  the  liver  as  glycogen  and  there- 
fore reaches  the  tissues  in  a  larger  stream  than  does  dextrose 
vmder  similar  circumstances,  and  hence  more  completely  re- 
places fat  as  the  source  of  energy.  In  a  later  paper  Johansson^ 
explains  that  after  ingesting  200  grams  of  dextrose  containing 
740  calories,  or  one-quarter  the  man's  energy  requirement  for  a 
day,  the  rise  in  carbon  dioxid  output  lasts  for  six  hours  and  then 
falls  to  the  fasting  basis.  This  is  an  indication  of  the  ready 
absorption  and  combustion  of  ingested  dextrose.  If  there  has 
been  prolonged  fasting  ingested  dextrose  may  cause  no  rise  in 
the  carbon  dioxid  output  in  man  on  account  of  its  conversion 
into  glycogen.     (See  p.  147.) 

The  truth  of  the  statement  that  carbohydrates  exactly 
replace  an  isodynamic  equivalent  of  fat  is  illustrated  by  Rubner's^ 
experiment  on  a  man  in  which  he  compared  the  production  of 
energy  in  starvation  with  that  produced  after  the  ingestion  of 
one  and  one-fifth  that  requirement  in  the  form  of  cane  sugar. 
For  the  sake  of  emphasis  the  metabolism  after  giving  one  and 
one-fifth  the  starvation  requirement  in  the  form  of  meat  is  also 
printed : 

Starvation 2042  calories. 

Sugar  (120  per  cent,  of  requirement) 2087  calories. 

Meat  (120  per  cent,  of  requirement) 2566  calories. 

It  has  been  seen  that  carbohydrates  ingested  alone  diminish 
the  protein,  metabolism.     This  reduces  the  specific  dynamic 

'  Johansson:  "Skandin.  Archiv  fur  Physiologic,"  1908,  Bd.  xxi,  p.  30. 
^Rubner:    " Encrgicgcsetzc,"  IQ02,  p.  410. 


178 


SCIENCE   OF   NUTRITION. 


action  of  protein  in  the  general  metabolism  and  the  small  specific 
dynamic  action  of  sugar  scarcely  changes  the  total  metabolism 
from  the  starvation  requirement. 

Any  excess  of  sugar  above  the  requirement  for  energy  is 
retained  in  the  body  either  in  the  form  of  glycogen  or  as  fat. 

The  contrast  given  above  between  the  results  of  the  ingestion 
of  carbohydrates  and  of  meat  is  extremely  striking. 

It  is  evident  that  the  carbohydrate  food  protects  protein 
tissue  from  waste  better  than  do  other  foodstuffs,  and  as  a 
source  of  energy  is  the  most  economical. 

When  carbohydrates  and  protein  are  ingested  together  in 
quantity  sufficient  for  the  requirement  of  the  organism,  it  has 
been  found  that,  taking  the  starvation  protein  metabolism  as 
one,  nitrogen  equilibrium  can  be  maintained  by  ingesting  one 
part  of  protein.^ 

The  work  of  Siven,^  however,  was  the  first  indication  that 
nitrogen  equilibrium  may  be  maintained  at  even  a  lower  level 
than  that  ordinarily  present  in  starvation.  A  somewhat  under- 
sized healthy  man  weighing  60  kilograms,  who  normally  ate  a 
mixed  diet  containing  16  grams  of  nitrogen,  was  given  less  and 
less  protein  and  an  attempt  was  made  to  establish  nitrogen 
equilibrium  at  lower  and  lower  levels.  The  daily  ration  was 
rich  in  carbohydrates  and  yielded  2444  calories.  This  must  have 
been  considerably  in  excess  of  the  requirement. 

The  experiment  was  divided  into  four  periods  of  about  a 
week  each,  which  may  be  summarized  as  follows : 


Length  in  Days. 


1,7 
11,8 

III,  6 

IV,  6 


N   IN   THE 

Food. 


12.69 

10.40 

8.71 

6.26 


Days  until  N 

Equilibrium 

WAS  Obtained. 


at  once 
3 


N  LOSS  BEFORE 

N  Equilibrium 
WAS  Obtained. 


0-S3 
0-34 

2.09 


Total  N  to 
Body. 


+  9-73 
+  6.04 

+  4.39 
-0.58 


^  E.  Voit  and  Korkunoff:  "  Zeitschrift  fur  Biologic,"  1895,  Bd.  xxxii,  p.  117. 
^  Siven:  "Skan.  Archiv  fiir  Physiologic,"  1900,  Bd.  x,  p.  91, 


INGESTION   OF   FAT   AND   CARBOHYDRATES.  1 79 

It  is  apparent  that  nitrogen  equilibrium  may  be  established 
after  ingesting  6.26  grams  of  nitrogen,  although,  as  has  been 
seen,  the  elimination  during  the  early  days  of  starvation  in  man 
is  usually  10  grams.  During  the  first  three  periods  of  reduced 
protein  intake,  as  much  as  20.16  grams  of  protein  nitrogen  were 
actually  added  to  the  body.  In  a  fifth  period  nitrogen  equilib- 
rium was  obtained  on  the  fourth  day  on  a  diet  containing  4.52 
grams  of  nitrogen. 

The  susceptibility  of  the  protein  metabolism  to  sudden 
withdrawal  of  carbohydrates  was  shown  by  Lusk  ^  upon  himself. 
Nitrogen  equilibrium  was  nearly  established  in  two  different 
experiments  at  different  levels,  with  the  ingestion  of  20.55  and 
9.23  grams  of  nitrogen  respectively.  In  the  first  experiment 
withdrawal  of  350  grams  of  carbohydrates  from  the  mixed  diet 
caused  a  rise  in  nitrogen  metabolism  from  19.84  to  27.00  grams, 
incurring  a  loss  of  body  nitrogen  of  6.45  grams.  In  the  second 
experiment  withdrawal  of  the  carbohydrates  increased  the  nitro- 
gen excretion  from  11.44  to  17.18,  a  loss  to  the  body  of  7.95 
grams.  The  losses  are  for  the  second  day  after  the  withdrawal 
of  the  carbohydrates,  since  the  metabolism  remains  under  the 
influence  of  the  glycogen  supply  during  the  first  day. 

Subsequent  experimentation  has  shown  that  partial  re- 
placement of  carbohydrates  by  fat  in  the  diet  may  have  no  in- 
fluence, or  only  a  transitory  one,  upon  the  amount  of  protein 
metabolized.  This  is  of  value  in  practical  dietetics.  Tallquist^ 
established  nitrogen  equilibrium  in  a  man  with  a  diet  containing 
about  16  grams  of  nitrogen,  10  per  cent,  of  the  calorific  value 
being  contained  in  protein  and  90  per  cent,  in  carbohydrates. 
On  replacing  one-third  of  the  carbohydrate  calories  in  the  diet 
with  fat  calories  an  increased  protein  metabolism  was  observed 
for  two  days,  followed  by  nitrogen  equilibrium  on  the  third  day. 
The  food  given  contained  35  calories  per  kilogram,  a  moderate 
quantity,  and  was  made  up  as  follows: 

Period    I.  16.27  g.  N  +    44.6  g.  Fat  +  466  g.  Carb.  =  2866  Cal. 
"     11.  16.08  g.  N  -I-  140. 1  g.  Fat  -I-  250  g.  Carb.  =  2873  Cal. 

'  Lusk:   "Zcilschrift  fiir  Biologic,"  1890,  Bd.  xxvii,  p.  459. 
^Tallquist:   "Archiv  fiir  Hygiene,"  1902,  Bd.  xli,  p.  177. 


l8o  SCIENCE    OF   NUTRITION. 

The  nitrogen  elimination  was  as  follows : 

Day.                                                  N  Excreted.  N  Balance. 

Period    I. — i 17. ii  — 0.84 

2 14.40  +1.86 

3 14-65  +1.62 

4 15-58  +0-69 

"     II.— s 17.66  —1.58 

6 17-32  —1.24 

7 15-94  +0.14 

8..: 16.22  0.14 

This  proves  that  with  a  diet  containing  i6  grams  of  nitrogen 
in  protein,  nitrogen  equilibrium  is  about  as  easily  maintained 
on  a  mixed  diet,  including  carbohydrates  and  fats,  as  when  only 
carbohydrates  are  allowed  with  the  protein. 

Incidentally  it  may  be  remarked  that  in  diseases  of  the  liver, 
such  as  catarrhal  jaundice,  hepatic  cirrhosis,  cholelithiasis  with 
jaundice  and  in  cases  of  engorgement  of  the  liver  more  carbohy- 
drates are  needed  to  maintain  nitrogen  equilibrium  than  normally 
is  the  case.^  Tallquist  warns  against  thinking  that  the  tendency 
towards  a  higher  protein  metabolism  here  manifested  is  due  to 
toxic  influences,  but  believes  that  the  cause  lies  in  the  fact  that 
glycogen  can  no  longer  be  effectively  stored  in  the  liver. 

The  sparing  influence  of  carbohydrate  oxidation  upon 
protein  metabolism  has  been  beautifully  illustrated  by  Lander- 
gren.^  Diets  containing  carbohydrates  and  fats,  but  scarcely 
any  nitrogen  (about  one  gram  daily),  were  given  men  and  the 
protein  metabolism  noted.  This  condition  is  called  that  of 
speci-fic  nitrogen  hunger.  After  four  days'  administration  of 
such  a  diet  the  urinary  nitrogen  may  be  reduced  to  less  than  four 
grams. 

In  one  experiment  in  which  this  was  accomplished  carbohy- 
drates were  entirely  replaced  by  fat  with  the  result  that  protein 
metabolism  rose  to  the  amount  found  in  starvation  (about  lo 
grams).  It  has  already  been  explained  that  ingestion  of  fat 
alone  will  not  affect  protein  metabolism  in  starvation.  The 
experiment  is  as  follows : 

*  Tallquist:   "Archiv  fiir  Hygiene,"  1908,  Bd.  Ixv,  p.  39. 

*Landergren:    "Skan.  Archiv  fiir  Physiologie,"  1903,  Bd.  xiv.  p.  112. 


III. 

IV. 

V. 

11.87 

3-95 
37-8 

13-7 
3-04 
45-0 

15-2 
4.2 

38-4 

INGESTION   OF   FAT   AND    CARBOHYDRATES.  181 

Carbohydrate  Period.  Fat  Period. 

Diet  =  45-2  Cal.  per  Kg.  Diet  =  43.7  Cal.  per  Kg. 

N  in  Urine.  N  in  Urine. 

Day  o *i2.y6  Day  5 4.28 

"   I ''   6 8.86 

"   2 "   7 9.64 

'    3 

"   4 3-76 

*  Ordinary  diet. 

On  day  5,  the  first  of  the  fat  diet,  it  is  evident  that  the  pro- 
tein metabolism  was  afi'ected  by  the  use  of  the  glycogen  supply 
of  the  body,  an  influence  which  became  negligible  on  the  second 
and  third  days  of  the  fat  diet  (p.  56). 

Landergren  gives  the  following  results  in  various  cases  of 
specific  nitrogen  hunger,  showing  the  nitrogen  in  the  urine 
before  the  diet,  and  after  four  days  thereof: 

II. 

N  in  urine  (ordinary  diet) 12.76 

N  in  urine  (specific  N  hunger) 3.76 

Calories  in  diet  per  kg 45.2 

This  reduction  of  protein  metabolism  to  four  grams  on  the 
fourth  day  was  brought  about  by  the  following  diets  in  the  dif- 
ferent cases: 

II.     750  g.  carbohydrates =  45.2  cal.  per  kg. 

III.     300  g.  carbohydrates  +  150  g.  fat =  37.8  "       "     " 

V.     380  g.  carbohydrates  -|-  150  "  "    =  38.4  "       "     " 

A  diet  containing  half  its  calories  in  carbohydrates  and  half 
in  fat  has  therefore  the  same  protein  protecting  power  as  one 
made  up  of  carbohydrates  alone.  This  demonstrates  the 
rationality  of  a  mixture  of  the  non-nitrogenous  foodstuffs. 

Landergren  finds  that  on  a  diet  containing  two-thirds  of  the 
calorific  requirement  the  urinary  nitrogen  on  the  fourth  day 
may  be  eight  grams,  or  nearly  the  fasting  quantity.  The  diet 
was  made  up  of — 

X.  240  g.  carbohydrate  +  64  g.  fat =   21.8  cal.  per  kg. 

Therefore,  in  specific  nitrogen  hunger  with  undernutrition,  the 
.nitrogen  eliminated  in  the  urine  appears  to  be  increased.  It  is 
a  pity  that  this  statement  rests  on  only  one  experiment,  for  it 
does  not  appear  in  accord  with  the  following  w^ork  of  Chittenden. 


l82 


SCIENCE    or   XUTSITION 


Chittenden^  finds  that  nitrogen  equilibriinn  may  "be  main- 
tained on  a  diet  containing  a  ven^  small  amoiont  of  protein  and 
two-thirds  of  the  bod5^'s  requirement  of  energ}'.  The  first  ex- 
periment was  on  Fletcher  and  lasted  six  days.  The  daily  ration 
contained  7.19  g.  nitrogen  +38.0  g.  fat  +  253  g.  carbohydrates = 
21.3  calories  per  kg.  The  excreta  contained  6.90  grams  of 
nitrogen  daUv.  On  this  diet  the  indi^^dual  showed  ''remarkable 
physical  strength  and  endurance." 

Another  experiment  was  performed  by  Chittenden  on  him- 
self and  lends  itself  for  interesting  comparison  with  tlie  results 
of  the  ingestion  of  a  maintenance  ration.  The  food  was  prin- 
cipally vegetable.     The  results  may  be  thus  tabulated : 


A  LOW  lea"t:l  of  xitrogex  equtt-trrtltm  in  nor]sial  and 

UNDERXT.-TRITION. 

Date. 

Diet. 

N  EXCXtETION. 

N  IN  Grams. 

Cat-  pee  Kg. 

Maxch  23 

March  2; 

6.79 
6.88 

34-7 
22.4 

6.56 

6.34 

+OJ23 
+0.54 

Nitrogen  equilibrium  may  therefore  be  maintained  at  a  low 
level  even  during  the  state  of  undernutrition  present  when  22.4 
calories  per  kilogram  are  in  the  daily  diet.  On  a  milk  diet 
Rubner^  found  that  the  ingestion  of  2483  grams  of  milk  con- 
taining 84  grams  of  protein  and  two-thirds  the  bodVs  require- 
ment of  energy  resulted  in  the  addition  of  6.7  grams  of  protein 
to  the  body  daily  for  three  days  (p.  224). 

It  is  a  valuable  piece  of  information  to  know  that  one  may 
diet  an  obese  patient  on  a  food  containing  little  protein  and  two- 
thirds  the  body's  energ}^  requirement  without  danger  of  pro- 
tein loss.  The  other  third  of  the  necessan^  energ}'  will  be  fur- 
nished by  the  body's  own  store  of  fat.     It  is  not  remarkable  that- 

^  CMttenden:   " Ptrsiological  Economy  in  Nutrition,"  1904,  pp.  14,  40. 
^  Rubner:   "Zeitschrift  fiir  Biologie,"  Bd.  xv,  1879,  p.  130. 


INGESTION   OF   FAT   AND    CARBOHYDRATES. 


183 


the  body  is  capable  of  great  physical  effort  on  such  a  diet,  for 
a  fasting  man  is  also  competent  in  this  direction  (p.  80). 

In  the  last  chapter  mention  was  made  of  the  sparing  action 
of  gelatin  on  protein  metabolism,  and  its  ingestion  was  found  to 
prevent  about  23  to  37.5  per  cent,  of  the  protein  loss  during 
starvation.  Murlin^  in  an  extensive  series  of  experiments  has 
shown  that  the  sparing  power  of  gelatin  is  greater  than  this  when 
it  is  ingested  with  a  mixed  diet.  He  finds  that  if  the  quantity  of 
nitrogen  eliminated  in  fasting  be  taken  as  one,  then  nitrogen 
equilibrium  may  be  maintained  in  dogs  and  in  man  on  ingestion 
of  a  diet  rich  in  carbohydrates  whether  the  nitrogen  of  the  diet 
be  protein  nitrogen  equal  to  one,  or  whether  it  contain  one-third 
protein  plus  two-thirds  gelatin  nitrogen.  This  is  shown  in  the 
following  experiment  on  a  man,  the  results  being  expressed  in 
averages  per  day. 


EFFECT  OF  SUBSTITUTING  GELATIN  FOR  PROTEIN  IN  A  MIXED 
DIET  IN  MAN. 

N  elimination  on  a  third  day  of  fasting  =  13.23  g. 


Source  of  N  in  Diet. 


All  protein  N 

Two-thirds  (63%)  gelatin  \ 
N  +  one-third  protein  N  / 
AU  protein  N 


3208 
3620 
3220 


jW 


47 
51 
46 


2  « 


14-25 

14-53 
14.26 


J^  <<  w 

~  H  < 
S  OS  pj 


^3-33 
13.82 

13-52 


O  OS 

Z^ 


4-0.87 

+0.71 

-fo.74 


Murlin^  also  showed  that  the  sparing  power  of  gelatin  was 
due  to  its  immediate  chemical  nature  and  not  to  the  sixty  per 
cent,  of  dextrose  which  can  arise  from  it  in  metabolism.  (See 
p.  132.)  For  example  a  fasting  dog  was  given  12  grams  of  dex- 
trose daily  for  four  days  after  thirteen  days  of  fasting;  then 
20  grams  of  gelatin  were  substituted  during  a  period  of  four 
days.     The. dextrose  scarcely  exerted  any  sparing  power  over 

*  Murlin:   "American  Journal  of  Physiolog)',"  1907,  vol.  xi.\,  p.  285. 
^  Murlin:   ".Vmerican  Journal  of  Physiologj',"  1907,  vol.  .\.\,  p.  234. 


1 84 


SCIENCE    OF   NUTRITION. 


the  protein  metabolism,  whereas  the  ingestion  of  gelatin  showed 
the  usual  sparing  of  31  per  cent. 

The  same  fact  was  demonstrated  on  a  man  who  was  brought 
into  nitrogen  equilibrium  on  an  adequate  mixed  diet  containing 
ID  grams  of  nitrogen  and  carbohydrates  enough  to  supply  fifty 
per  cent,  of  the  energy.  The  state  of  nitrogen  equilibrium  was 
not  quite  maintained  on  substituting  gelatin  for  two-thirds  of 
the  protein  nitrogen  in  the  diet.  Murlin  explained  this  as  being 
due  to  a  dislike  for  sweets  on  the  part  of  the  individual  so  that 
he  could  not  take  carbohydrates  in  large  excess.  However,  when 
the  nitrogen  of  the  diet  was  reduced  so  as  to  contain  only  protein 
nitrogen  equal  to  one-third  that  eliminated  in  fasting,  together 
with  the  sixty  per  cent,  of  dextrose  which  could  have  originated 
from  the  gelatin  previously  ingested,  the  waste  of  body  nitrogen 
rose  far  above  that  observed  when  gelatin  and  protein  were 
given.     The  experiment  may  thus  be  presented. 


INFLUENCE  OF  GELATIN  IN  METABOLISM. 
Figures  are  for  the  last  day  of  each  period. 


Source  of  N  in  Diet. 


AU  protein  N 

Two-thirds  (67%)  gelatin 
N  -|-  one  third  protein  N 
One-third  protein  N 


^0 

K 
W 

< 

Q 
0 
0 

s 

0  s 

u 

^ 

w 

4 

I97I 

43 

10.05 

IO-3S 

6 

1935 

42 

9.62 

10.12 

3 

1858 

40 

3-23 

5.62 

-0.30 
-0.50 

-2-39 


Here  the  rise  in  the  metabolism  of  body  protein  corresponds 
to  the  withdrawal  of  gelatin  from  the  diet  even  in  the  presence 
of  a  considerable  intake  of  carbohydrate.  Hence  Landergren's^ 
interpretation  that  the  rise  in  nitrogen  elimination  which  takes 
place  on  changing  from  a  pure  carbohydrate  to  a  pure  fat  diet, 
is  due  to  the  body's  absolute  requirement  for  carbohydrate  and 
that  it  obtains  this  by  increasing  its  protein  metabolism  is 
scarcely  tenable. 

1  Landergren:  Inaugural  Dissertation,  1902:  "  Maly's  Jahresbericht,"  1902, 
p.  685. 


INGESTION   OF   I  AT   AND  CARBOHYDRATES.  1 85 

The  true  explanation  of  these  experiments  will  be  apparent 
after  a  discussion  of  Rubner's  work  concerning  the  "wear  and 
tear"  quota,  which  follows  at  the  end  of  the  chapter.  /'See  p.  i86.; 
It  will  then  be  evident  that  the  "wear  and  tear"  quota  of  protein 
metabolism  must  be  covered  by  the  ingestion  of  an  equal  amount 
of  "repair"  quota,  while  the  additional  "dynamic"  quota  may 
be  supplied  by  protein  or  by  gelatin.  Murlin  foimd  that  the  "  re- 
pair" quota  was  best  administered  in  the  form  of  beef  heart,  and 
that  the  proteins  of  biscuit  meal  were  very  inefficient  as  sparers  of 
body  protein. 

In  the  course  of  his  experiments  Murlin  found  that  the  longer 
the  animal  had  fasted,  that  is,  the  lower  its  protein  condition,  the 
more  readily  did  gelatin  reduce  the  waste  of  body  protein. 

Murlin  also  showed  that  three-quarters  of  the  stan-ation 
nitrogen  ingested  as  gelatin  and  one-quarter  as  protein  were  not 
able  to  maintain  nitrogen  equilibrium  in  the  dog.  Two-thirds 
the  starvation  nitrogen  requirement  ingested  as  gelatin  and  one- 
third  as  protein  maintain  nitrogenous  equilibrium-  Carbohy- 
drates ingested  alone  reduce  protein  metabolism  to  one-third 
that  found  in  stanation.  One-third  the  stanation  quantit)' 
seems  to  be  the  limit  of  protein  metabolism  compatible  with  life- 
It  may  also  be  noted  that  in  a  fasting  diabetic  dog  the  protein 
metabolism  may  rise  to  five  fold  that  noted  in  simple  fasting 
(see  p.  285)  or  fifteen  fold  the  irreducible  minimum  of  the  "wear 
and  tear"  quota.  Under  these  circumstances  the  writer  has 
found  that  pure  gelatin  given  alone  is  more  effective  as  a  protein 
sparer  than  it  is  in  simple  fasting.  Thus  after  giving  30  grams 
of  gelatin  to  a  fasting  phlorhizinized  dog  the  following  results 
were  obtained  on  analyzing  the  urine  every  twelve  hours: 

Dxxntasc  N.  Boor  X. 

Fastins.  i:  hoars 12-5*  3-77  —3-77 

Gelatii  ;  =  4.644  g.  N;  12  hours 20.66  6.02  — 1.37 

Fasting,  12  hours 3-79  ^3-79 

If  the  fecal  nitrogen,  which  is  very  smaU  after  gelatin  in- 
gestion, be  negleaed,  it  may  be  calculated  that  body  protein 


1 86  SCIENCE    OF   NUTRITION. 

was  spared  to  the  extent  of  63.7  per  cent,  after  the  administration 
of  gelatin,  instead  of  30  per  cent,  as  in  ordinary  fasting.  One 
may  therefore  conclude  that  the  great  waste  of  body  protein 
which  takes  place  in  diabetes  belongs  in  Rubner's  category  of 
"d)Tiamic"  protein  metabolism,  for  which  gelatin  may  be 
largely  used  as  a  substitute. 

Since  carbohydrates  so  effectively  spare  protein  from  com- 
bustion it  would  seem  logical  that  their  use  should  render  the 
retention  of  protein  in  the  body  easier  than  when  fat  is  given 
with  protein. 

Liithje^  finds  a  long  continued  nitrogen  retention  in  man 
when  much  nitrogen  in  protein  is  ingested  (up  to  50  g.  N  daily !) 
and  carbohydrates  and  fat  making  a  total  of  4000  calories  or 
66  calories  per  kilo.     (See  also  Bomstein's  experiment,  p.  no.) 

In  a  subsequent  paper  Liithje^  finds  that  the  P2O5  retention 
in  convalescence  is  that  which  corresponds  to  the  retention  of  pro- 
tein for  the  formation  of  new  tissue  including  bone.  Some- 
times in  a  healthy  person  not  enough  P2O5  is  retained  to  build 
up  "flesh,"  and  the  protein  retained  must  therefore  exist  in  the 
form  of  "deposit  protein."  This  protein,  he  says,  is  not  stored 
in  the  blood,  for  the  composition  of  the  blood  does  not  alter; 
but  is  perhaps  retained  in  the  cellular  fluids,  just  as  glycogen  is 
retained  by  the  cells. 

Rubner^  has  lately  given  attention  to  the  protein  requirement 
of  the  cells.  Reference  has  already  been  made  (p.  74)  to  the 
"wear  and  tear"  quota  represented  by  the  protein  metabolism 
of  a  dog  maintained  on  a  diet  of  pure  fat  in  quantity  sufficient  to 
cover  the  requirement  for  energy.  This  quota  is  reduced  when 
carbohydrates  are  ingested  so  that  it  may  amount  to  only  four 
per  cent,  of  the  total  energy  requirement.  The  following 
statements  hold  true  if  an  animal  be  given  the  maintenance 

^Liithje:   "Zeitschrift  fiir  klinische  Medizin,"  1902,  Bd.  xliv,  p.  22. 

^Liithje:  "Deutsches  Archiv  fiir  klinische  Medizin,"  1904,  Bd.  Ixxxi,  p. 
278. 

^Rubner:    "Archiv  fiir  Hygiene,"  1908,  Bd.  Ixvi,  p.  45. 


INGESTION   OF   FAT   AND    CARBOHYDRATES.  1 87 

requirement  of  energy  in  the  form  of  non-nitrogenous  food- 
stuffs. Otherwise  if  protein  be  ingested  it  will  itself  be  used  to 
supply  the  energy  requirement  (compare  with  work  of  Schulz,  p. 
76).  The  "wear  and  tear"  quota  must  be  covered  by  the  in- 
gestion of  a  "repair  quota."  Ingestion  of  protein  beyond  the 
amount  needed  for  the  repair  of  the  normal  waste  may  first  be 
used  for  growth.  The  portion  used  for  growth  is  called  the 
"growth"  quota  and  is  dependent  on  the  protein  condition  of 
the  cells .  The  conditions  which  determine  the  ' '  wear  and  tear 
metabolism  and  those  which  determine  growth  are  entirely 
dissimilar,  although  without  metabolism  growth  is  impossible. 
If  protein  be  administered  beyond  the  requirement  of  the  cells 
for  repair  and  for  growth,  then  the  excess  constitutes  a  "  dynamic  " 
quota  which  after  deamination  serves  to  furnish  energy  to  the 
cells  in  the  same  fashion  as  do  fat  and  sugar. 

Rubner  states  that  the  greater  the  impoverishment  of  the 
protein  supply  in  an  animal  fed  with  fat,  the  more  powerful  is 
the  protective  effect  of  small  quantities  of  ingested  protein  over 
the  loss  of  body  protein.  Also  the  retention  of  protein  depends 
on  the  protein  content  of  the  animal  as  well  as  on  the  quantity 
of  protein  ingested.     This  is  illustrated  in  the  following  table. 

INFLUENCE   OF  THE   PROTEIN   CONTENT  OF  A  DOG  ON  THE 
RETENTION  OF  PROTEIN  INGESTED. 
Total  N  Content  N  in  Terms  of  100  N  in  Dog 

OF  Dog.  in  Food.  to  Body. 

318.8 5-25  +1-65 

354-7 5-57  +i-°2 

310.6 6.72  4-2.64 

363.7 12.79  +2-62 

It  is  evident  from  this,  that  of  the  same  diet  of  protein  more 
will  be  retained  when  the  nitrogen  content  of  the  dog  is  low 
■  than  when  it  is  high;  and  also  that  a  small  protein  intake  may 
cause  the  same  retention  of  nitrogen  as  a  large  protein  intake, 
if  in  the  first  instance  there  be  a  relative  impoverishment  of  the 
protein  content  of  the  animal. 

According  to  these  laws  adult  cells  which  have  been  depleted 


1 88  SCIENCE    OF   NUTRITION. 

of  their  protein  may  gradually  improve  their  nutritive  condition 
until  they  reach  an  optimum,  at  which  point  they  lose  their 
power  to  attach  additional  protein. 

The  question  arises,  To  what  extent  may  the  amino-bodies 
formed  within  the  intestine  be  regenerated  into  protein?  It  is 
believed  that  the  cells  of  the  intestinal  villus  regenerate  fat  from 
fatty  acid  and  glycerin,  since  neutral  fat  alone  is  found  in  the 
thoracic  duct.  But  all  the  starch  fed  is  not  regenerated  into 
starch,  nor  is  maltose  regenerated  into  maltose  in  the  body. 
Much  may  be  burned  as  dextrose  and  only  a  part  is  transformed 
into  glycogen.  Long  ago  Schultzen  and  Nencki^  stated  that 
a  certain  portion  of  the  amino-bodies  formed  in  digestive 
proteolysis  was  absorbed  and  oxidized,  and  that  the  absorbed 
protein  itself  followed  the  lines  of  an  enzymotic  cleavage  into 
amino-bodies.  In  the  light  of  newer  knowledge  several  author- 
ities have  recently  elaborated  theories  along  similar  lines.  It 
has  been  pointed  out  by  Folin^  that  there  is  little  evidence  of 
reconstruction  of  all  the  protein  ingested.  He  cites  the  experi- 
ments of  Nencki  and  Zaleski,^  which  showed  that  the  portal 
blood  during  digestion  contains  four  times  as  much  ammonia 
as  arterial  blood,  and  that  the  mucosa  of  both  stomach  and 
intestine  yields  large  quantities  of  ammonia.  The  inference  is 
that  the  ammonia  of  the  portal  vein  is  derived  from  ammonia 
produced  in  the  mucosa  as  well  as  from  that  which  normally 
originates  in  the  intestine  during  tryptic  proteolysis. 

Modern  theory  suggests  the  deamination  of  the  larger 
part  of  the  amino-acids  formed  in  intestinal  digestion 
within  the  intestinal  wall  itself.  It  is  possible  that  the 
"dynamic"  quota  of  Rubner  is  always  so  treated  instead 
of  being  first  converted  into  serum  proteins  in  accordance  with 
Abderhalden's  ideas.     The  "repair"  quota  and  the  "growth" 

^Schultzen  and  Nencki:   "Zeitschrift  fur  Biologic,"  1872,  Bd.  viii,  p.  124. 

^  Folin:  "American  Journal  of  Physiology,"  1905,  vol.  xiii,  p.  117. 

_^_Nencki  and  Zaleski:    " Zeitschrif t  f iir  physiologische  Chemie,"  1901,  Bd. 
xxxiii,  p.  206. 


INGESTION  OF   FAT  AND   CARBOHYDRATES.  1 89 

quota  must,  however,  be  furnished  either  in  the  form  of  blood 
proteins  or  of  amino-acids  which  have  passed  the  intestines. 
It  is  well  known  that  the  nutritive  condition  of  the  cells  de- 
termines the  passage  of  fat  from  the  fat  repositories  in  the  body, 
and  it  may  be  questioned  whether  the  nutritive  condition  of  the 
cells  may  not  determine  either  the  passage  of  amino-acids 
through  the  intestinal  wall  (or  their  synthesis  within  it),  instead 
of  their  deamination  there.  If  at  times  the  amino-acids  pass 
through  the  intestinal  wall  into  the  blood  stream,  as  the  work 
on  "  amino-sugars "  (pp.  123  and  124)  renders  probable,  then 
their  s}Tithesis  to  new  protein  might  be  accomplished  in  the 
liver,  in  muscle  or  possibly  in  all  tissue. 

The  conditions  of  protein  metabolism  are  entirely  similar 
to  those  of  starch  metabolism:  (i)  digestive  hydrolysis;  (2) 
partial  combustion  of  the  end-products;  and  (3)  possible 
regeneration  of  portions  of  the  end  products  into  substances 
akin  to  the  originals  but  characteristic  of  the  organism, — i.  e., 
glycogen  and  body  proteins.  In  the  case  of  proteins  the  second 
or  metabolic  process  involves  the  production  of  sugar  and  of 
fatty  acids  from  the  amino-acids  involved.  The  third  or  re- 
generative process  is  promoted  by  such  a  protein  as  casein,  which 
yields  a  large  variety  of  cleavage  products. 

In  conclusion,  it  may  be  said  that  carbohydrates  are  the 
most  economical  of  the  foodstuffs,  both  physiologically  and 
financially.  They  are  the  greatest  sparers  of  protein.  In- 
gestion of  fat  has  for  its  object  the  relieving  of  the  intestine 
from  excessive  carbohydrate  digestion  and  absorption.  Inges- 
tion of  fat  in  too  large  quantities^ leads  to  digestive  disturbances, 
and  if  carbohydrates  are  entirely  abandoned,  to  acetonuria. 


CHAPTER  VIII. 

THE  INFLUENCE  OF  MECHANICAL  WORK  ON 
METABOLISM. 

In  the  account  of  metabolism  during  starvation,  a  short 
description  has  already  been  given  of  the  influence  of  mechanical 
vi^ork  on  protein  metabolism,  of  the  influence  of  posture  on 
general  metabolism,  and  of  the  relation  of  the  amount  of  metabo- 
lism to  the  diurnal  variations  of  human  temperature. 

The  source  of  mechanical  work  must  be  from  metabolism, 
for  mechanical  energy  cannot  be  derived  from  nothing.  The 
necessary  energy  might  be  obtained  in  one  of  two  ways,  either 
at  the  expense  of  a  proportionate  reduction  in  the  quantity  of 
heat  liberated  by  the  resting  organism,  or  by  an  increase  in  the 
amount  of  the  metabolism.  In  the  former  case  work  would 
diminish  the  heat  production,  and  might  cool  the  tissues,  which 
is  not  observed  to  take  place.  If  work  were  done  at  the  expense 
of  increased  metabolism,  and  if  this  increase  were  completely 
converted  into  mechanical  effect,  then  the  heat  production  in  the 
organism  might  remain  the  same  as  in  the  resting  state.  If, 
however,  the  result  of  mechanical  effort  be  a  stimulation  of  me- 
tabolism to  the  extent  of  not  only  enabling  the  body  to  do  work, 
but  also  causing  it  to  produce  more  heat  than  when  at  rest, 
then  the  tendency  of  the  tissues  must  be  to  grow  warmer,  per- 
haps with  a  resulting  outbreak  of  sweat  to  reduce  the  body 
temperature  through  physical  regulation.  The  last  named 
is  the  actual  process. 

Lavoisier's  discovery  that  the  absorption  of  oxygen  is  in- 
creased during  mechanical  exercise,  firmly  established  the  fact 
of  a  higher  metabolism  under  these  conditions. 

The  first  experiments  in  which  the  effect  ofjwork  upon  the 


MECHANICAL   WORK   ON  METABOLISM. 


191 


total  metabolism  was  demonstrated  were  made  upon  a  man  by 
Pettenkofer  and  Voit.^  A  man  turned  an  ergostatic  wheel 
7500  revolutions  on  each  working  day  for  a  period  of  nine 
hours,  which  afforded  sufficient  exercise  to  cause  great  fatigue 
at  the  end  of  the  day.  The  experiments  were  made  both  dur- 
ing hunger  and  when  the  man  was  ingesting  a  medium  mixed 
diet.    The  food  supplied  in  the  mixed  diet  contained : 


Graus. 

Protein 121. 7 

Fat 117. 

Carbohydrates 352. 


Calories. 

506 

1088 

1443 


Total 3037 

The  metabolism  of  this  man,  a  strong  workman,  weighing 
seventy  kilograms,  at  rest  and  at  work,  starving  or  on  the  medium 
mixed  diet  as  given  above,  is  presented  in  the  following  table  :^ 

EFFECT   OF   MECHANICAL   WORK   ON   METABOLISM  IN   MAN. 


Grams  Metabolized. 

Cal.  of 
Metab- 
olism. 

Cal. 

ABOVE 

Fasting 
Quantity. 

Experiment 
No.  OF  Pet- 
tenkofer 

AND  VOIT. 

Protein. 

Fat. 

Car- 
bohy- 
drates. 

Starvation — Rest  ... 
—Rest  . . . 
—Work  . . 

70.8 
68.7 
66.1 

222 
208 
387 

2374 
2231 
3882 

1582 

I 
III 
IV 

Mixed  Diet— Rest . . 

—Rest . . 

"          —Rest . . 

—Work  . 

—Work  . 

121. 7 
118.7 
125.0 
121. 7 
122.0 

73 
93 
84 

208 

152 

352 
352 
352 
352 
352 

2638 
2714 
2750 
3856 
3378 

33(> 
412 

458 
1554 
1076 

V 

VI 

VII 

VIII 

IX 

From  these  early  experiments  it  was  evident  that  mechanical 
work  did  not  increase  protein  metabolism  even  in  starvation, 

'  Pettenkofer  and  Volt:   "Zeitschrift  fiir  Biologic,"  1866,  Bd.  ii,  p.  537. 

'  I  have  multiplied  the  nitrogen  of  the  ingesta  and  excreta  by  6.25  to  obtain 
the  quantity  of  the  protein  given  and  metabolized.  The  ratio  N  :  C  =  i  :  3.28 
in  protein  has  been  employed.  The  dry  starch  has  been  calculated  as  con- 
taining 44.2  per  cent,  and  the  fat  as  containing  76.5  per  cent,  of  carbon,  which 
were  the  figures  used  by  Pettenkofer  and  Voit.  Rubner's  standard  calori- 
metric  values  have  been  used.     (See  Introductory  Chapter.) 


192  SCIENCE   OE  NUTRITION. 

but  that  the  power  to  do  work  might  readily  be  supplied  by  the 
increased  metabolism  of  fat. 

It  is  interesting  to  note  the  increase  of  the  metabolism  above 
the  fasting  minimum  in  the  above  circumstances.  This  rela- 
tion is  embodied  in  the  following  table : 

Calories  of 
Metabolism.        Increase. 

Starvation — Rest  (average) 2302 

—Work 3882  1582 

Medium  diet — Rest  (average) 2717  415 

—Work 3856  1554 

"             — Work 3378  1076 

This  table  indicates  a  specific  dynamic  action  of  the  food 
amounting  to  415  calories.  Another  conclusion  may  be  drawn 
from  the  table,  and  one  which,  if  true,  is  of  importance;  it  is 
that  during  the  working  days  the  specijic  dynamic  action  of  the 
food  does  not  appear.  In  other  words  the  metabolism  during 
work  on  a  mixed  diet  is  not  greater  than  during  starvation  when 
the  same  amount  of  work  is  being  effected.  It  may  be  that  the 
free  heat  liberated  as  the  result  of  the  specific  dynamic  action 
of  the  food  can  be  utilized  in  warming  the  cells  in  the  service  of 
the  production  of  mechanical  energy,  just  as  it  is  used  in  lieu 
of  the  heat  produced  through  chemical  regulation.  If  this  be 
true,  giving  protein  to  men  at  work — for  example,  athletes — 
would  not  entail  economic  waste  of  the  fraction  usually  lost 
when  it  is  given  during  rest, 

Rubner^  shows  that  a  man  of  seventy  kilograms  weight, 
developing  mechanical  energy  to  the  extent  of  15,000  kilogram- 
meters  per  hour,  produces  practically  the  same  quantity  of  car- 
bon dioxid,  no  matter  what  the  temperature  of  his  environment 
may  be.     The  results  of  the  experiment  are  as  follows: 

Percentage      Carbon  Dioxid  Water  Ex- 

Temperature  Moisture  in  per  Hour  creted  per  Hour 

OF  THE  Air.  the  Air.  in  Grams.  in  Grams. 

7.4°  81  84.0  58.0 

12.7°  84  78.5  70.8 

16.7°  59  97.0  138.1 

17-5°  87  84-5  90-4 

18.8°  83  81.2  112.8 

25.0°  47  78.7  230.0 

^Rubner:  Von  Leyden's  Handbuch,  "Die  Ernahrungstherapie,"  1903, 
Bd.  i,  p.  74. 


MECHANICAL   WORK   ON  METABOLISM.  1 93 

This  person  while  at  rest  and  at  a  temperature  of  21.1°  ex- 
creted 33.6  grams  of  carbon  dioxid  and  42  grams  of  water. 

It  is  clear  that  during  work  the  metabolism  -is  independent 
of  surrounding  temperature,  of  climatic  conditions.  In  other 
words,  during  mechanical  work  the  influence  of  the  ^'chemical 
regulation"  0}  body  temperature  may  be  eliminated.  (See  p.  92.) 
The  extra  heat  production  in  doing  mechanical  work  is  utilized 
instead  of  the  production  of  heat  which  is  excited  reflexly  through 
cold.     These  results  were  forecast  by  Voit.^ 

Generally  speaking,  neither  clothing  nor  temperature  affects 
the  amount  of  the  metabolism  during  exercise.  They  influence 
only  the  quantity  of  water  eliminated  in  the  perspiration,  in 
the  effort  of  the  body  to  maintain  its  normal  temperature  through 
physical  regulation.  It  is  evident  from  Rubner's  details  of  the 
water  excretion  that  at  a  low  temperature  the  extra  heat  pro- 
duction during  mechanical  exercise  is  lost  by  radiation  and 
conduction.  Rubner  explains  that  the  slight  increase  in  the 
excretion  of  w^ater  above  that  lost  while  at  rest,  is  due  to  its 
increased  evaporation  through  increased  respiratory  activity. 
At  a  higher  temperature  conduction  and  radiation  become 
insufficient  to  cool  the  body,  and  a  large  proportion  of  the 
loss  of  heat  takes  place  at  the  expense  of  the  evaporation  of 
sweat. 

In  hot,  moist  climates,  however,  the  cooling  of  the  body 
through  the  evaporation  of  moisture  becomes  difficult,  and  this 
is  especially  pronounced  in  the  case  of  fat  people  (p.  103),  who 
with  difficulty  discharge  the  heat  produced  within  them.  Broden 
and  Wolpert^  show  the  effect  of  the  action  of  temperature  and 
humidity  on  the  metabolism  of  a  fat  man,  weighing  loi  kilo- 
grams, who  executed  the  same  amount  of  mechanical  work 
under  various  conditions  of  experimentation.  The  work  was 
light,  being  5375  kilogrammeters  per  hour.  The  results  were 
as  follows: 

•  Voit:   "Zeitschrift  fur  Biologic,"  1878,  Bd.  xiv,  p.  152. 

*  BnxJcn  and  Wol|jLrt:    "Archiv  fur  Hygiene,"  1901,  Bd.  xxxix,  p.  298. 

13 


194 


SCIENCE    or   NUTRITION. 


EFFECT  OF  WORK,  TEMPERATURE,  AND  HUMIDITY  ON  THE 
METABOLISM  OF  A  FAT  INDIVIDUAL. 


Grams  per  Hour. 

Temperature. 

Dry  Air. 

Humid  Air. 

CO2  in  Grams 
per  hour. 

H2O  in  Grams 
per  hour. 

COjin  Grams 
per  hour. 

H2O  in  Grams 
per  hour. 

20° 

47.8 
47-3 
50-3 

319  +  38  g. 
sweat. 

46.4 
48.0 
60.7 

28-^0° 

^6-^.'^° 

269 

+ 
266  g. 
sweat. 

This  individual  was  the  same  already  mentioned,  p.  103, 
and  the  explanation  given  there  is  equally  applicable  here.  In 
a  dry  climate  the  same  amount  of  mechanical  work  may  be  ac- 
complished by  a  fat  person  at  both  20°  and  30°  without  changing 
the  metabolism.  At  a  temperature  of  37°  the  metabolism  rises, 
for  the  cooling  power  of  the  evaporating  sweat  does  not  seem 
sufficient  to  act  through  the  dense  covering  of  fat.  This  action 
is  intensified  in  moist  air,  where  the  evaporation  of  water  is 
hindered.  Under  these  latter  conditions  the  small  amount  of 
work  was  accomplished  only  at  the  expense  of  great  discomfort 
and  profuse  perspiration. 

The  obese  therefore  work  under  great  disadvantage  in  a  hot, 
and  especially  in  a  hot  and  moist,  climate.  The  profuse  per- 
spiration explains  their  desire  for  water  to  drink. 

In  the  early  experiments  of  Pettenkofer  and  Voit,  already 
cited,  it  was  shown  that  work  did  not  raise  the  protein  metabol- 
ism even  in  starvation,  and  that  the  source  of  the  power  ap- 
peared to  be  the  increased  combustion  of  the  non-nitrogenous 
fat. 

In  other  experiments  a  slight  rise  in  the  nitrogen  metabolism, 
continuing  into  the  day  following  work,  has  been  noted.  The 
protein  metabolism,   however,    is  not   sufficient  to   yield   the 


MECHAXIC.\L   WORK   ON  METABOLISM. 


195 


energ}'  necessan'  for  a  hard  day's  work.  In  the  well  kno^vTi 
experiments  of  Fick  and  Wislicenus^  the  authors  climbed  the 
Faulhorn,  in  Switzerland,  a  mountain  1956  meters  high.  The 
product  of  their  weight  into  the  height  to  which  they  raised 
themselves  gave  them  the  work  done.  The  experimenters  took 
their  last  nitrogenous  food  seventeen  hours  before  starting  on 
their  walk.  They  climbed  for  six  hours  and  collected  the  urine 
of  this  period  and  that  of  seven  hours  thereafter.  Their  re- 
sults were  as  foUows: 


Urinary  iDynamic  Value       Body        Height  of  Faul- 
JM  OF  13  I  OF  N  IN  Kgm.     Weight.  horn. 

HRS. 


Fick 

Wislicenus 


5-74 
S-S4 


63,378 
61,280 


66 
76 


1956  meters. 
1956  meters. 


Work  in 
Kgm. 


129,096 
148,656 


The  work  accomplished  represents  three  times  the  energy 
liberated  from  the  protein  metabolism  of  the  time.  The  output 
of  energy  as  measured  above  was  not  all  the  increase  in  the 
amount  of  mechanical  energy  during  the  period,  for  the  heart 
and  respiratory  muscles  acted  with  greater  force,  and  energy 
was  expended  by  swinging  the  arms  and  by  friction  on  the 
road. 

The  fact  observed  by  Pettenkofer  and  Voit  that  protein 
metabolism  may  not  be  appreciably  affected  during  mechanical 
work  has  been  abundantly  confirmed  by  Krummacher.^  A 
porter  weighing  79  kilograms  was  given  a  diet  containing  3700 
calories,  14.28  grams  of  protein  nitrogen  and  a  large  amount 
of  carbohydrate.  The  man  turned  a  dynamometer  and  pro- 
duced 402,000  kilogrammetcrs  of  work.  The  slight  increase 
in  protein  metabolism  could  have  yielded  but  three  per  cent, 
of  the  energy  required  for  the  work.  Krummachcr  states  that 
protein  metabolism  may  increase  during  work  only  when  the 


*  Fick  and  Wislicenus:   " Myothermische  Untersuchungen,"  1889. 
'Krummachcr:    "Zeitschrift  fiir  Biologic,"  1896,  Bd.  xxxiii,  p.  108. 


196  SCIENCE    OF   NUTRITION. 

non-nitrogenous  fat  and  carbohydrates  become  less  available 
in  metabolism.  We  have  already  seen  that  protein  metabolism 
rises  in  the  absence  of  carbohydrates.  It  may  be  that  with  the 
exhaustion  of  carbohydrates  during  exercise,  a  period  ensues 
when  the  loss  of  their  influence  leads  to  an  increased  protein 
destruction.  The  larger  the  quantity  of  carbohydrates  given  the 
less  marked  would  be  this  influence.  It  is  interesting  in  this 
connection  that  soldiers  when  starting  on  a  march  may  have  a 
high  respiratory  quotient  (indicating  the  combustion  of  carbo- 
hydrates) which  falls  at  the  end  of  the  march  (fat  combustion) 
and  which  may  remain  lower  than  at  first,  even  on  a  day  fol- 
lowing the  march.^  The  fact  that  mechanical  work  may  be  ac- 
complished at  the  expense  of  an  increased  combustion  of  fat 
and  carbohydrates  should  not  cause  one  to  forget  that  protein  may 
become  the  sole  source  of  energy  in  the  body.  It  has  already 
been  shown  that  a  fasting  animal,  after  burning  all  his  fat,  main- 
tains his  life  on  protein  alone  (p.  73),  and  that  Pfliiger  kept  a 
dog  in  active  condition  on  meat  alone.  As  protein  may  yield 
58  per  cent,  of  sugar,  this  substance  may  still  be  the  principal 
source  of  energy. 

The  following  experiment  not  only  indicates  the  fully  proved 
point  that  muscular  work  does  not  increase  protein  metabolism 
but  it  also  shows  that  the  character  of  the  protein  metabolism  is 
unchanged  hy  muscular  activity.  Shaffer^  has  given  a  man  a 
diet  which  was  free  from  purins  and  which  contained  only 
5.9  grams  of  nitrogen.  The  individual  spent  the  greater  part 
of  six  days  in  bed  as  a  rest  period  (I).  He  then  occupied 
himself  for  five  days  with  laboratory  work,  which  gave  a  normal 
period  (II).  During  a  final  period  (III)  of  four  days  he  worked 
in  the  laboratory  and  performed  in  addition  such  mechanical 
work  as  that  of  walking  ten  miles.  The  average  of  the  analyses 
of  the  urines  of  the  three  periods  are  given  below. 

^  Zuntz  and  Schumburg:   "Physiologic  des  Marsches,"  1901. 

^Shaffer:   "American  Journal  of  Physiology,"   1908,  vol.  xxii,  p.  445. 


MECHAOTCAL   WORK  ON   METABOLISM. 


197 


UNCHANGED   CHAIL\CTER  OF  THE  URINE  AFTER  MUSCULAR 

WORK. 


Food. 

Urine. 

Period. 

N 

Calories. 

Nitrogen  as: 

Sulphur: 

Total. 

4-77 
4.40 

3-94 

Ammonia.    Creatinin.        P"'^ 
-    Acid. 

Rest. 

Total. 

I.  Rest.... 

II.  Normal 
III.  Work   .. 

5-9 
6.0 

5-9 

2300 
3000 
3200 

0.35      j      0.605         O-II 
0.38      '      0.60         !   0.106 
0.42            0.56        1   0.12 

0-35 
0.42 
0.42 

0.438 
0.424 
0.414 

Shaffer  concludes  that  if  sufficient  food  be  allowed,  an 
increase  or  decrease  of  muscular  activity  has  no  effect  on  protein 
metabolism  as  indicated  by  the  various  quantities  of  nitro- 
genous end-products  which  appear  in  the  urine.  Shaffer 
agrees  with  Hoogenhuyze  and  Verploeg^  that  with  adequate 
nourishment  the  creatinin  elimination  is  unaffected  by  muscular 
work. 

Bomstein^  reports  continual  retention  of  ingested  protein 
during  seventeen  days'  work,  at  a  time  when  only  protein  was 
administered.  The  quantity  of  protein  given  was  large,  con- 
taining 19.96  grams  of  N,  and  the  daily  work  accomplished 
was  moderate,  being  17,000  kilogrammeters.  The  nitrogen 
retention  amounted  to  1.475  grams  daily,  or  an  addition  of  800 
grams  of  "flesh"  to  the  body  in  seventeen  days. 

Loewy^  reaches  the  same  conclusion  that  long  continued 
muscular  exercise  favors  protein  retention.  This  suggests  the 
basis  of  muscular  hypertrophy  due  to  physical  exercise. 

Large  protein  ingestion,  however,  is  not  apparently  essential 
to  the  full  maintenance  of  physical  power.  This  has  been  shown 
by  Chittenden,^  who  maintained  soldiers  and  athletes  in  physical 

'Hoogenhuyze  and  Veqdocg:  "Zcitschrift  fur  physiologischc  Chcmie," 
1905,  Bd.  xlvi,  p.  415. 

^  liornstein:   "Pfluger's  Archiv,"  1901,  Bd.  Ixxxiii,  p.  540. 

^  Loewy:   "Archiv  fiir  Phy.siologic,"  1901,  p.  299. 

'Chittenden:   "Physiological  Economy  in  Nutrition,"  1905. 


igS  SCIENCE    OF   NUTRITION. 

training  for  months  at  a  time  on  diets  containing  between  seven 
and  ten  grams  of  nitrogen,  or  about  half  what  the  average  man 
takes  if  the  question  be  left  to  his  taste  (see  p.  213). 

It  is  evident  that  the  power  to  accomplish  muscular  work  is 
not  usually  derived  from  protein  metabolism,  but  from  the  com- 
bustion of  the  non-nitrogenous  sugar  and  fat. 

Therefore,  physical  exercise  requiring  fat  consumption  with- 
out concomkant  destruction  of  protein  must  be  of  the  greatest 
value  in  the  treatment  of  obesity. 

The  problem  at  once  arises:  What  is  the  relative  value  of 
fats  and  carbohydrates  as  fuel  for  the  production  of  mechanical 
energy  by  the  body? 

Zuntz,^  from  experiments  made  by  Heineman,  calculates 
that  when  carbohydrates  predominate  in  a  man's  diet  an 
amount  of  energy  above  the  resting  requirement  is  liberated 
which  equals  9.33  calories  for  every  kUogrammeter  of  work  ac- 
complished, whereas  when  fat  is  given  10.37  calories  are  liberated 
in  the  performance  of  the  same  amount  and  the  same  kind  of 
work.  The  work  was  done  by  turning  the  wheel  of  an  ergostat. 
Since  one  kilogrammeter  is  the  mechanical  equivalent  of  2.35 
calories,  it  is  evident  that  25  per  cent,  of  the  total  excess  of  energy 
developed  by  work  is  convertible  into  mechanical  effect,  the 
balance  being  dissipated  as  heat.  Similar  experiments  made  by 
Zuntz  on  himself  showed  that  9.39  and  9.33  calories  of  meta- 
bolism were  liberated  on  a  fat  diet,  10.37  ^^^  10.41  on  a  carbo- 
hydrate diet,  when  one  kilogrammeter  of  work  was  accomplished. 

There  seems  to  be  little  difference  in  the  efficacy  of  the  body 
as  a  machine,  whether  fat  or  carbohydrates  are  used  as  fuel. 

Heineman^  remarks  that  Chauveau's  idea  that  fat  must  be 
first  converted  into  sugar  before  being  available  for  mechanical 
work  can  scarcely  be  valid,  for  such  a  conversion  of  fat  carbon 
into  sugar  would  entail  a  minimum  loss  of  energy  available  for 
mechanical  work  of  29  per  cent. 

^  Zuntz:   "Pfliiger's  Archiv,"  1900,  Bd.  Ixxxiii,  p.  557. 
^Heineman:   Ibid.,  p.  476. 


MECHANICAL  WORK  ON  METABOLISM.         1 99 

Atwater  and  Benedict^  thought  that  they  had  confirmed  these 
resuhs,  although  unfortunately  the  diets  provided  were  not 
strictly  protein  and  carbohydrate-protein,  but  were  really 
mixed  diets. 

Thus  J.  W.  C,  during  two  periods  of  twenty-two  days  each, 
ingested  day  by  day  diets  which  produced  the  following  meta- 
bolism as  calculated  from  the  body's  excreta: 

Calculated  Metabolism. 

Period  I.  Period  II. 

Carbohydrate  Diet.  Fat  Diet. 

Protein 434  calories.  489  calories. 

Fat 1288       "  3190       " 

Carbohydrates 3371       "  1465       " 

Total  metabolism 5093  5i44 

The  average  of  work  accomplished  and  body  heat  evolved 
each  day,  as  measured  in  the  Atwater  calorimeter,  were  as 
follows : 

Work  and  Metabolism  as  Directly  Measured. 

Carbohydrate  Diet.  Fat  Diet. 

Mechanical  work 543  calories.  550  calories. 

Body  heat 4593       "  4555       " 

Total  metabolism 5136  S^^S 

The  work  was  done  on  a  stationary  bicycle.  It  is  evident  that 
the  work  could  not  have  been  at  the  expense  of  protein  metabol- 
ism. But  it  is  also  plain  that  the  work  could  have  been  derived 
from  carbohydrate  combustion  even  on  the  "fat"  diet  of 
Period  II. 

These  experiments,  however,  were  the  first  to  demonstrate 
exactly  that  mechanical  work  was  done  at  the  expense  of  a 
dynamic  equivalent  of  metabolism, — a  splendid  confirmation  of 
the  law  of  the  conservation  of  energy. 

In  one  other  experiment  Atwater  and  Benedict  calculated  for 
J.  W.  C.  a  metabolism  amounting  to  9981  calorics,  divided  as 

'Atwater  and  Benedict:  "Experiments  on  the  Metabolism  of  Matter  and 
Energy  in  the  Human  Body,"  1903,  U.  S.  Dept.  of  Agriculture,  Bulletin  136. 


200  SCIENCE    OF   NUTRITION. 

follows:  Protein,  478  calories;  fat,  7744  calories;  carbohy- 
drates, 1759.  The  man  worked  for  sixteen  hours  on  the 
bicycle.  The  work  done  measured  an  equivalent  of  1482 
calories;  the  body  heat  production  was  7382  calories,  both  of 
which  were  measured  in  the  Atwater  calorimeter,  and  the  total 
■energy  loss  reached  9314  calories,^  a  height  of  metabolism 
attained  also  by  Maine  lumbermen^  actively  employed  (p.  221). 
Later  work  by  Benedict  and  Carpenter^  includes  an  experi- 
ment upon  a  professional  bicycle  rider,  who  rode  the  stationary 
bicycle  in  the  respiration  apparatus.  The  results  per  hour 
may  be  thus  expressed: 

Calories  per  Hour. 

Metabolism  during  rest ^ 92. 

"  "       work 619. 

Increased  metabolism  due  to  work 527 

Heat  equivalent  of  work  accomplished 112 

Mechanical  efficiency  in  per  cent,  {-^jj  X  100) 21.3% 

The  rider  was  hard  pressed  and  working  at  a  maximum 
during  this  effort.  One  may  calculate  the  mechanical  work 
accomplished  as  being  13  kilogrammeters  per  second.  If 
this  work  can  be  compared  to  the  work  accomplished  by  bicycle 
riders  in  a  six-day  competition  when  the  individual  sometimes 
remains  on  the  track  for  23  out  of  the  24  hours  it  may  be  seen 
that  the  metabolism  in  such  cases  may  readily  exceed  10,000 
calories  daily. 

Although  the  work  accomplished  by  the  professional  rider 
amounted  to  double  and  treble  that  accomplished  by  four  less 
experienced  individuals,  the  mechanical  efficiency  of  the  differ- 
ent riders  hardly  varied  from  the  general  average  of  20.8  per 
cent.  This  recalls  the  statement  of  Johansson  and  Koraen 
(see  p.  202)  that  the  increased  output  of  carbon  dioxid  due  to 

^  The  calories  calculated  from  the  metabolism  and  those  directly  measured 
by  the  calorimeter  did  not  exactly  agree  in  this  particular  instance — an  exception 
in  a  brilliant  series. 

^  Woods  and  Mansfield:  U.  S.  Dept.  of  Agriculture,  1904,  Bulletin  149. 
^  Benedict  and  Carpenter:  U.  S.  Dept.  of  Agriculture,  Office  of  Experiment 
Stations,  Bulletin  208,  1909. 


MECHANICAL    WORK   ON   METABOLISM.  20I 

mechanical  work  is  always  directly  proportional  to  the  work 
accomplished. 

.Although  from  Zimtz's  work  it  seems  proved  that,  in  fur- 
nishing power  for  mechanical  work,  carbohydrates  and  fat  are 
replaceable  one  for  the  other  according  to  their  dynamic  values, 
there  is  a  well-founded  belief  that  work  may  be  obtained  in 
larger  quantity  from  an  individual  if  carbohydrates  be  available. 

Schumburg^  finds  that  ingestion  of  carbohydrates  enables 
a  fatigued  muscle  to  contract  more  powerfully.  Hellsten^ 
states  that  in  doing  mechanical  work  in  the  morning  before 
breakfast,  an  improved  capacity  occurs  thirty  to  forty  minutes 
after  ingesting  sugar. 

The  ready  exhaustion  of  diabetics  who  cannot  burn  dextrose 
confirms  this  observation. 

Lee  and  Harrold^  have  found  evidences  of  great  fatigue  in 
the  excised  muscles  of  a  cat  from  which  the  readily  combustible 
sugar  had  been  removed  by  rendering  the  cat  diabetic  with 
phlorhizin.  Another  cat  similarly  treated,  the  body  of  which, 
however,  had  been  flooded  with  sugar  by  ingestion  before  the 
animal  was  killed,  showed  a  much  larger  capacity  for  muscular 
contraction. 

The  writer*  while  injecting  phloretin  solutions  into  the 
jugular  vein  of  fasting  rabbits,  diabetic  through  phlorhizin, 
noticed  that  seven  out  of  eight  rabbits  had  convulsions,  while 
normal  rabbits  were  not  so  affected.  Four  died  and  three  lost 
motor  control  of  the  muscles  of  their  limbs.  In  these  three 
there  was  an  increased  dextrose  elimination  in  the  urine  on 
account  of  the  passage  of  the  glycogen  content  of  the  organs 
into  the  blood,  which  glycogen  would  normally  be  immediately 
available  for  muscular  activity  (p.  79).  The  animals  which 
survived   the   convulsions   obtained   control   of   their   muscles 

'  Schumburg:  "  Archiv  fur  Physiologic,"  1896,  p.  537. 
'  Hellsten:   "Skan.  Archiv  fur  Physiologic,"  1904,  Bd.  xvi,  p.  139. 
»Lee  and   Harrold:    Proceedings  of  the  American  Physiological  Society, 
"American  Journal  of  Physiology,"  1900,  vol.  iv,  p.  ix. 

*Lusk:  "Zeitschrift  fur  Biologic,"  1898,  Bd.  xxxvi,  p.  109. 


202  SCIENCE    OF   NUTRITION. 

in  two  to  four  hours.  This  indicates  a  slow  preparation  from 
fat  of  materials  available  for  the  production  of  muscle  work. 

Schumburg^  finds  that  coffee  and  tea  have  no  recuperative 
power  over  the  muscles  of  a  fatigued  organism,  except  when 
taken  with  other  foods,  and  that  the  stimulating  action  of  al- 
cohol is  only  temporary.  Hellsten,^  exercising  before  breakfast, 
finds  that  the  effect  of  taking  tea  is  almost  negligible,  and  that 
the  effect  of  alcohol  is  at  first  to  increase  the  muscle  power,  but 
that  after  twelve  to  forty  minutes  there  is  a  decrease  in  power 
which  lasts  for  two  hours.  No  such  depression  occurs  after 
taking  sugar.  It  is  obvious  that  alcohol  is  not  beneficial  when 
muscular  work  is  to  be  accomplished. 

The  carbon  dioxid  produced  as  a  result  of  mechanical  work 
is  quickly  eliminated  through  the  lungs.  Higley  and  Bowen^ 
find  that  the  increased  elimination  begins  twenty  seconds  after 
the  commencement  of  bicycle  riding  and  reaches  its  maximum 
in  about  two  minutes.  At  this  point  it  remains  constant  from 
minute  to  minute  provided  the  same  amount  of  work  is  done. 
This  principle  has  been  frequently  demonstrated  by  Zuntz  and 
his  pupils.  It  is  evident,  however,  that  the  quantity  of  carbon 
dioxid  excretion  for  the  unit  of  work  accomplished  will  be  less 
during  starvation  and  on  a  fat  diet  than  when  carbohydrates 
are  ingested,  by  reason  of  the  higher  heat  value  of  fat  carbon.^ 

Johansson  and  Koraen^  have  caused  a  man  to  raise  a  weight 
of  21.7  kilograms  one  half  meter  high,  each  movement  lasting 
one  second  and  there  being  in  different  experiments  300,  600, 
720,  and  900  movements  per  hour.  In  the  trained  individual  the 
quantity  of  increase  in  the  carbon  dioxid  expired  was  exactly, 
proportional  to  the  number  of  the  movements  in  the  unit  of 

^  Schumburg:    Loc.  cit.  ^Hellsten:    Loc.  cit. 

^  Higley  and  Bowen:  "American  Journal  of  Physiology,"  1904,  vol.  xii,  p.  335. 

^Johansson  and  Koraen:  "Skand.  Archiv  fiir  Physiologie,"  1902,  Bd. 
xiii,  p.  251. 

^Johansson  and  Koraen:  "Skandin.  Archiv  fiir  Physiologie,"  1903,  Bd. 
xiv,  p.  60. 


MECHANICAL   WORK   ON  METABOLISM.  203 

time.     The  experiments  were  performed  when  food  was  absent 
from  the  intestines. 

It  has  already  been  shown  that  25  per  cent,  of  the  total  energy 
of  the  increase  above  the  resting  metabolism  as  caused  by  work 
is  converted  into  mechanical  energy  by  a  person  turning  the 
wheel  of  an  ergostat  with  his  arms. 

Katzenstein^  has  sho\ATi  a  still  more  economical  utilization  of 
the  fuel  when  the  work  accomplished  is  climbing,  about  35  per 
cent,  of  the  total  increase  in  metabolism  being  then  converted 
into  mechanical  effect.  Walking,  the  commonest  muscular  ex- 
ercise, is  accomplished  with  the  greatest  mechanical  efficiency- 

A  great  many  interesting  details  have  been  worked  out  in 
Zuntz's  laboratory  by  his  pupils.  The  following  epitome  of 
long  investigations  shows  the  comparative  energy  equivalents 
necessary  for  dog,  horse,  and  man  to  move  one  kilogram  of 
body  weight  one  meter  with  a  given  rapidity  along  a  horizontal 
plane  or  to  lift  one  kilogram  of  body  weight  one  meter  high.^ 
The  experiments  were  made  by  placing  the  individual  on  a 
moving  platform,  the  speed  and  incline  of  which  could  be  varied. 

A  study  of  the  table  on  p.  204  will  show  that  it  requires  much 
less  energy  for  a  horse  to  move  one  kilogram  of  his  weight  one 
meter  horizontally  than  for  a  dog  to  do  the  same  at  the  same 
velocity.  It  also  appears  that  a  man  of  small  weight  requires 
more  energy  to  a  unit  of  substance  than  a  man  of  large  size. 
This  rule  has  been  confirmed  in  dogs  by  Slowtzoff,'  who  shows 
that  energy  amounting  to  0.529  kilogrammeter  is  required  for 
one  meter  horizontal  motion  by  a  dog  weighing  37  kilograms, 
and  1. 138  kilogrammcters  by  a  dog  weighing  5.5  kilograms. 
Slowtzoff  does  not  find  that  this  variation  is  proportional  to  the 
skin  area  of  the  animal. 

The  table  also  shows  that  there  is  little  variation  in  the  dog, 

'  Katzcnstein:    "Pfliigcr's  Archiv,"    1891,   Bd.   xlix,   p.   379. 
*  Frentzcl  and  Reach:    Ibid.,   1901,  Bd.  Ixxxiii,  p.  494. 
•Slowtzoff:  "Pfliiger's  Archiv,"  1903,  Bd.  xcv,  p.  190. 


204 


SCIENCE    OF    NUTRITION. 


horse,  and  man  in  the  amount  of  energy  necessary  to  raise  one 
kilogram  of  body  substance  one  meter  high. 

ENERGY  REQUIREMENTS  OF  DIFFERENT  ANIMALS  IN  PER- 
FORMANCE OF  THE  SAME  AMOUNT  OF  MECHANICAL 
WORK. 


Animal. 


Dog... 
Dog... 
Horse. 
Man.. 


Normal  locomotion 

F. 
Slow  locomotion    . . 

R. 
Normal 

R. 
Slow 


Energy  Requirement 

IN    KiLOGR AMMETERS. 

Velocity  in 

Meters 

PER    MlN- 

For  moving 

horizontally 

I  Kg.  I 

Meter. 

For  raising  i 

Kg.  I  Meter 

High. 

Horizontal 
Movement. 

26.9 
26.9 

0.495 
0.501 

2-954 
3-259 

}    78-57 

456.8 

0-137 

2.912 

78-57 

55-5 

0-334 

2-857 

74-48 

72.9 

0.217 

3.190 

71-32 

67.9 

O.211 

3.140 

71.46 

80.0 

0.288 

3-563 

51-23 

88.2 

0.263 

3-555 

42-34 

72.6 

0.284 

2.913 

62.04 

81. 1 

0.231 

2.921 

60.90 

80.0 

0.244 

2.729 

56-54 

86.5 

0.219 

■    2.746 

66.94 

86.5 

0.233 

35-92 

65.8 

0.230 

!•  2.846 

63-95 

65.8 

0.251 

J 

34-58 

1 

Incline  of 
Road  in  Per 
Cent.  During 
Climbing  Ex- 
periment. 


17.2 

10.3 
9-6-13-3 
6-5 

30.7-62. 
23-30-5 

(■    23.3 


It  is  possible  to  calculate  the  food  ration  for  a  march  if  the 
figures  given  in  the  table  be  employed.  If  it  be  assumed  that 
a  man  weighing  70  kilograms  travels  74.4  meters  a  minute,  he 
will  accomplish  4.46  kilometers  or  2.7  miles  per  hour.  If  it 
requires  the  energy  equivalent  of  0.217  kilogramme ters  to  move 
one  kilogram  of  his  weight  one  meter,  it  will  require  67,747  kilo- 
grammeters  (0.217  X  70  X  4460)  to  move  him  4.46  kilometers, — 
67,747  kilogrammeters  being  equivalent  to  159.205  calories. 
This  is  the  equivalent  of  17.1  grams  of  fat,  which  may  be  added 
to  the  maintenance  resting  dietary  requirement  to  supply  the 
energy  necessary  for  an  hour's  quiet  walk  on  a  level  road.     If 


MECHANICAL   WORK  ON  METABOLISM.  205 

the  road  be  inclined  so  that  the  man  raises  himself  500  meters 
during,  the  hour's  walk,  the  metabolism  will  be  still  further  in- 
creased. The  work  of  ascent  will  be  his  weight  multiplied  by 
the  height  of  his  climb,  or  35,000  kilogrammeters.  The  expen- 
diture of  energ}'  by  the  body  in  order  to  accomplish  this  work  is 
threefold  the  work  done,  or  105,000  kilogrammeters,  which 
equals  246.75  calories,  or  26.5  grams  of  fat.  The  hour's  walk 
in  this  case  would  require  the  production  of  an  energy  equiva- 
lent, above  the  resting  metabolism,  amounting  to  that  contained  in 
43.6  grams  of  fat, — that  is,  17. i  grams  for  a  forward  locomotion 
of  4.46  kilometers  and  26.5  grams  to  lift  the  body  to  an  altitude 
of  500  meters. 

In  the  last-mentioned  table  it  is  seen  that  there  is  an  increase 
in  the  metabolism  for  a  unit  of  horizontal  motion  when  the 
progress  of  the  individual  is  very  slow.  This  is  explained  by 
the  fact  that  speed  of  progress  was  half  the  normal,  was  unusual, 
and  forced. 

The  rule  is  that  the  metabolism  increases  with  speed  in  men 
(0.39  to  0.84  per  cent,  per  meter  increase  between  60  and  100 
meters  per  minute)  and  in  horses  (1.03  per  cent,  per  meter  in- 
crease above  78  meters  per  minute),  but  this  is  not  seen  in  dogs.^ 

Katzenstein^*  finds  that  the  metabolism  during  the  descent 
of  a  mountain  is  less  by  10  per  cent,  than  the  increase  caused  by 
walking  on  a  level  surface.  The  muscles  which  act  to  inhibit  a 
too  rapid  descent  are  not  required  to  be  so  active  as  those  which 
give  forward  impetus  to  the  body  on  a  level  road. 

This  idea  has  recently  been  still  further  investigated  by 
mountaineers^  who  compared  the  actual  heat  production  with 
the  energy  of  metabolism  during  one  minute,  for  horizontal 
motion,  and  for  ascent  and  descent  of  a  mountain  path  which 
had  a  25  per  cent,  incline.     The  results  were  as  follows: 

'  Zuntz:   "Pfluger's  Archiv,"  1903,  Bd.  xcv,  p.  192. 
*  Katzenstein:   hoc.  cii.,  p.  376. 

'  Zuntz,  Locwy,  Mullcr,  and  Caspar! :  "Holunklima  und  Bcrgwandcrungon 
in  ihrcr  Wirkung  auf  den  Mcnschen,"  1906. 


2o6  SCIENCE   OF   NUTRITION. 

Ascent  28.8      Horizontal        Descent 
Meters.        100  Meters.      76  Meters. 

Calories  of  energy  of  metabolism '.69.3  67.8  40.8 

Calories  of  heat  liberated 46.9  67.8  85.5 

The  smallest  liberation  of  heat  occurred  during  the  ascent 
of  the  mountain  at  the  time  when  the  energy  of  metabolism  was 
being  converted  into  energy  of  position. 

The  largest  heat  production  occurred  during  the  descent  of 
the  mountain.  The  metabolism  was  the  least,  but  energy  of 
position  was  converted  into  heat  through  the  vibration  of  the 
body  at  each  footfall. 

Zuntz  and  Schumburg^  show  that  a  well-placed  knapsack 
is  carried  by  a  soldier  with  very  little  increased  expenditure  of 
energy.  A  soldier  weighing  74.45  kilograms,  moving  at  the  rate 
of  74.4  meters  per  minute,  requires  541.8  calories  for  the  move- 
ment of  one  kilogram  of  substance  1000  meters.  The  same 
soldier,  laden  with  a  knapsack  weighing  19  kilograms  (total 
weight  =  93-45  kilograms),  requires  only  502.3  calories  to  move 
one  kilogram  1000  meters.  A  pack  may  therefore  be  more 
economically  moved  than  the  body's  substance,  which  is  an 
argument  against  obesity. 

Zuntz  and  Schumburg  find  an  increase  in  the  metabolism 
of  a  marching  soldier  if  the  knapsack  be  badly  placed,  or  if 
the  body  be  sore  and  weary. 

Lavonius^  finds  the  maximum  amount  of  work  attainable 
by  a  trained  wrestler  of  great  reputation  to  be  the  equivalent 
of  30  kilogrammeters  per  second. 

A  subject  of  very  great  interest  is  the  result  of  training.  It 
is  well  known  that  if  a  cobbler,  for  example,  be  removed  from 
his  trade  and  be  compelled  to  climb  a  mountain,  he  will  at  first 
be  of  little  use  as  compared  with  a  Swiss  guide.  But  after  con- 
stant practice  the  blood-vessels  dilate  at  once  in  response  to  the 
needs  of  the  muscles  and  the  heart  expends  less  energy;  un- 

^  Zuntz  and  Schumburg:  "Studien  zu  einer  Physiologie  des  Marsches," 
Berlin,  1901. 

*  Lavonius:   "Skan.  Archiv  fiir  Physiologie,"  1905,  Bd.  xvii,  p.  196. 


MECHANICAL   -WORK   ON  METABOLISM. 


207 


necessary  motions  with  the  arms  and  legs  are  diminished  in 
number;  the  strain  for  the  accomphshment  of  a  given  piece  of 
work  diminishes ;  the  thorax  enlarges  to  promote  readier  respira- 
tion; the  man  becomes  "trained,"  and  there  may  be  a  les- 
sened metabolism  for  the  fulfillment  of  a  definite  amount  of 
work. 

The  experimental  measurements  of  the  efhcacy  of  the 
working  organism  as  described  above  were  made  on  well-trained 
men,  a  difference  on  account  of  training  having  been  early 
recognized  by  Zuntz. 

Certain  differences  between  the  urine  of  trained  and  untrained 
men  have  already  been  noted  (p.  68). 

Biirgi^  made  some  investigations  upon  an  individual  before 
and  after  training  for  mountain  climbing.  The  ascents  were 
made  at  different  altitudes  on  the  roadbed  of  mountain  railways, 
and  the  carbon  dioxid  elimination  was  measured.  The  results 
are  shown  in  the  following  table: 

EFFECT  OF  "TRAINING"  ON  METABOLISM. 


Place. 

Altitude  in 
Meters. 

Incline  of 
Road  in  per 

CENT. 

CO2  Excretion  per  Kgm.  of 
Work. 

Untrained. 

Trained. 

Brienz 

Gomergrat 

Brienz 

Gomergrat 

620 
2987 

690 
3021 

17.29 

19-3 
19.0 

19-3 

2.430 
2. 711 
2.251 
2-445 

2.103 
2.268 
2.063 
2. 117 

It  is  evident  from  this  that  a  trained  mountaineer  accom- 
plishes his  work  at  the  expense  of  less  metabolism  than  does  the 
untrained.  Also  that  at  a  moderately  high  altitude  (3000 
meters  =  522  mm.  of  mercury,  barometric  pressure)  the  trained 
organism  is  as  efficient  for  mechanical  work  as  at  the  sea  level; 
whereas  the  untrained  man  requires  a  much  greater  metabolism 

*  Biirgi:  "Archiv  fur  Physiologic,"  1900,  ]).  509. 


2o8  SCIENCE    OF   NUTRITION. 

to  accomplish  a  unit  of  work  at  the  higher  altitude  than  at  the 
lower. 

At  still  higher  altitudes  there  is  always  an  increase  in  the 
amount  of  metabolism  necessary  to  accomplish  mechanical 
effort,  and  this  will  be  discussed  in  another  chapter. 

Another  fact  of  importance  is  that  the  eifect  of  training 
especially  affects  the  muscles  involved  in  the  particular  move- 
ment, and  not  those  which  do  not  contract.  Thus  Zuntz^  found 
that  a  dog  trained  for  horizontal  motion  on  a  level  street  required 
1 1 79  small  calories  to  move  one  kilogram  body  weight  looo 
meters  and  7.668  small  calories  to  raise  one  kilogram  body  weight 
one  meter  high.  The  dog  was  then  gradually  trained  to  ascend 
an  incline.  After  two  years  he  required  only  5.868  small  calories 
to  lift  one  kilogram  one  meter,  but  he  required  1343  small  cal- 
ories per  kilogram  for  horizontal  locomotion  through  1000  meters. 
Therefore  the  specifically  trained  muscles  work  more  economi- 
cally than  those  which  are  at  the  time  but  little  used. 

A  man  trained  for  mountaineering  will  often  find  himself 
uncomfortable  when  walking  on  a  level  road.  The  mountaineer 
will  not  find  the  bicycle  an  easy  means  of  locomotion,^  nor  will 
the  bicyclist  unscathed  essay  the  mountain. 

A  benefit  derived  from  riding  a  horse  is  the  shaking  of  the 
internal  organs,  which  is  also  achieved  by  descending  a  steep 
pathway.  This  may  be  beneficial  to  the  life  processes  in  such 
a  comparatively  immobile  organ  as  the  liver  for  example.  It 
also  appears  to  promote  a  freer  evacuation  of  the  bowels. 

In  swimming  there  is  considerable  respiration  gymnastic?.^ 
The  water  pressure  upon  the  thorax  is  the  equivalent  of  the 
weight  of  an  8-kilogram  sand-bag,  which  the  swimmer  seeks  to 
counterbalance  by  increasing  the  pressure  in  his  lungs  through 
puffing  with  his  lips.  By  turning  over  on  the  back  the  swimmer 
removes    this    respiratory    influence.     Cold    water    stimulates 

^  Zuntz:    "Pfliiger's   Archiv,"    1903,    Bd.    xcv,    p.    200. 
^  Concerning  energy  expended  in  bicycle  riding  see  Berg,  Du  Bois-Reymond 
and  L.  Zuntz:  "Archiv  fiir  Physiologic,"  Supplement,  1904,  p.  20. 
^  R.  du  Bois-Reymond,  Ibid.,  1905,  p.  253. 


MECHANICAL   WORK  ON  METABOLISM,  209 

metabolism  (p.  loi),  but  the  effect  of  the  salt  in  ordinary  sea 
water  is  certainly  negligible. 

There  can  be  little  doubt  that  exercise,  especially  in  the  open 
air,  strengthens  the  organism  and  therefore  tends  to  prolong  life. 
Sometimes  muscular  exercise  is  mistakenly  considered  as  favor- 
ing intellectual  activity.  Yet  college  presidents  are  not  selected 
from  the  ranks  of  prize-fighters. 


14 


CHAPTER  IX. 
A  NORMAL  DIET* 

The  principles  of  metabolism  have  been  sufficiently  ex- 
plained in  the  foregoing  chapters  to  make  it  possible  to  under- 
stand the  basis  of  a  diet  which  shall  be  physiologically  rational. 

It  has  been  seen  that  the  average  starvation  metabolism  of  a 
vigorous  man  at  light  work  and  weighing  70  kilograms  approxi- 
mates 2240  calories,  or  32  calories- per  kilogram.  It  is  obvious 
that  this  quantity  of  energy  must  be  contained  in  the  daily  food, 
and  a  little  more  to  counterbalance  the  "specific  dynamic"  or 
heat- increasing  power  of  the  foodstuffs,  if  the  individual  is  to  be 
maintained  in  calorific  equilibrium.  It  has  been  seen  that 
when  an  average  mixed  diet  is  ingested  the  maintenance  require- 
ment is  between  ii.i  and  14.4  per  cent,  above  the  starvation 
minimum  (p.  162).  This  would  amount  to  from  2488  to  2562 
calories,  or  from  35.5  to  36.6  calories  per  kilogram  of  body 
weight  in  the  case  of  the  individual  just  referred  to. 

Rubner^  is  authority  for  the  following  table  which  indicates 
the  energy  requirement  of  men  of  various  weights  while  doing 
light  work. 

Weight  Area  in  Calories  of  Calories 

IN  Kg.  Sq.  M.  Metabolism.         per  Kg. 

80 2.283  2864  35.8 

70 2.088  2631  37.7 

60 1.885  2368  39.5 

50 1.670  2102  42.0 

40 1.438  1810  45.2 

Since  man  through  clothing  shuts  himself  off  from  the  reflex 
action  of  cold  on  the  skin,  the  greatest  factor  which  tends  to 
increase  his  metabolism  is  mechanical  work,  and  the  total  cal- 

*  Rubner:  von  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1903,  Bd.  i, 
P-  153- 

210 


A   NORMAL   DIET.  211 

ones  required  is  here  dependent  on  the  kind  and  the  amount  of 
the  work  accomplished.  The  requirements  in  this  regard  have 
already  been  discussed. 

A  point  of  great  interest  is  that  of  the  proper  proportion  in 
which  the  individual  foodstuffs  should  be  put  together  in 
making  up  a  ration. 

Voit  defines  a  food  as  a  well-tasting  mixture  of  foodstuffs  in 
proper  quantity  and  in  such  a  proportion  as  will  least  burden 
the  organism.     What  is  the  proper  proportion? 

Voit^  gives  the  following  ration  for  the  use  of  an  average 
laborer,  such  as  a  soldier  in  a  garrison, — that  is,  for  a  man  at 
work  from  eight  to  ten  hours  a  day:  Protein,  ii8  grams;  car- 
bohydrates, 500  grams;  fat,  56  grams.  This  diet  contains 
3055  calories. 

Such  a  ration  means  the  food  actually  ingested.  It  is  also 
assumed  that  the  foodstuffs  are  administered  in  a  digestible 
form,  and  are  therefore  completely  assimilable.  It  has  already 
been  pointed  out  in  the  Introductory  Chapter  that  the  feces 
contain  no  undigested  protein  when  good  food  is  given.  It 
is  therefore  fallacious  to  deduct  the  nitrogen  of  the  feces  from  the 
nitrogen  of  the  ingesta  in  order  to  determine  the  amount  of 
protein  assimilated.  Fecal  nitrogen  plus  urinary  nitrogen  to- 
gether represent  the  waste  of  assimilable  protein  nitrogen  (see 

P-  45)- 

The  allowance  of  118  grams  of  protein  has  provoked  much 
discussion.  The  original  figures  were  obtained  by  Voit  by  aver- 
aging the  protein  metabolism  of  many  laboring  men.  This 
requirement  of  protein  was  therefore  obtained  by  the  statistical 
method,  which  simply  showed  what  the  average  laborer  in  habit 
destroyed.  For  the  same  class  of  artisan,  the  diet  given  by 
Rubncr  calls  for  127  grams  of  protein;  by  Atwater  125  grams; 
and  Lichtcnfelt^  confirms  Voit's  average  as  being  the  quantity 
of^rotein  taken  by  laborers  in  northern  Italy. 

'Voit:   "Physiologic  dcs  Stoffwechsels,"  1881,  p.  519. 
*_Lichtcnftlt:   "Pfliiger's  Archiv,"  1903,  Bd.  xcix,  p.  i. 


212  SCIENCE    OF   NUTItlTION. 

For  men  at  hard  labor,  such  as  soldiers  in  the  field,  even 
higher  quantities  of  protein  are  commended, — by  Voit,  145 
grams;  by  Rubner,  165  grams;  by  Atwater,  150  grams.  These 
figures  again  are  based  on  statistics.  Quite  recently  Woods  and 
Mansfield^  found  that  the  average  protein  in  the  ration  of  fifty 
lumbermen  is  164  grams. 

In  striking  contrast  to  this  Siven^  at  the  age  of  thirty-one 
and  a  half  years  and  weighing  65  kilograms,  finds  he  can  main- 
tain himself  in  nitrogen  equilibrium  for  a  short  period  on  a  diet 
containing  between  4  and  5  grams  of  nitrogen,  or  25  to  31  grams 
of  protein.  In  fact,  in  one  experiment  the  food  contained  4 
grams  of  nitrogen,  of  which  2.4  grams  only  were  in  15.4  grams 
of  true  protein  and  the  balance  in  amino-acids  and  other  nitro- 
genous non-protein  matter  of  vegetable  origin.  Here  nitrogen 
equilibrium  was  nearly  attained,  the  nitrogen  ingested  being  4, 
and  that  excreted  4.28  grams.  The  food  given,  which  was  rich 
in  carbohydrates,  contained  2717  calories,  or  43  calories  per  kilo- 
gram, and  the  total  metabolism  as  estimated  by  respiration  ex- 
periments indicated  a  heat  production  of  2082  or  32  calories  per 
kilogram.  Here  was  practically  nitrogen  equilibrium  main- 
tained at  the  minimum  level,  and  a  low  total  metabolism  which 
was  largely  at  the  expense  of  carbohydrates. 

It  will  be  recalled  that  the  quantity  of  nitrogen  in  the  urine 
in  the  average  fasting  man  who  has  been  previously  well  nour- 
ished is  10  grams,  a  minimum  which  is  reducible  only  by  carbo- 
hydrate ingestion. 

The  experiments  of  Siven  did  not  satisfy  people  that  a  low 
protein  metabolism  was  compatible  with  continued  health  and 
strength.  Munk^  and  Rosenheim*  both  found  that  dogs  given 
a  quantity  of  protein  sufficient  only  to  maintain  nitrogen  equilib- 
rium gradually  lost  strength  and  became  afflicted  with  diges- 

^ Woods  and  Mansfield:  "Studies  of  the  Food  of  Maine  Lumbermen," 
U.  S.  Department  of  Agriculture,  1904,  Bulletin  149. 

^  Siven:  "Skan.  Archiv  fiir  Physiologie,"  1901,  Bd.  xi,  p.  308. 
^  Munk:   "Archiv  fiir  Physiologie,"  1891,  p.  338. 
*  Rosenheim:  Ihid.,  p.  341. 


A   NORMAL    DIET. 


213 


tive  disturbances.  These  experiments  fortified  the  idea  of  the 
benefits  to  be  derived  from  a  diet  containing  more  protein  than 
was  necessary  for  the  maintenance  of  nitrogen  equilibrium — 
a  luxus  consumption.  Rubncr  declares  that  a  large  protein 
allowance  is  the  right  of  civilized  man. 

The  tradition  that  a  continued  liberal  allowance  of  protein 
in  a  diet  is  a  prerequisite  for  the  maintenance  of  bodily  vigor 
has  been  dispelled  by  Chittenden^  and  his  co-workers,  of  whom 
Mendel  is  the  most  prominent. 

Professor  Chittenden  had  suffered  from  persistent  rheuma- 
tism of  the  knee-joint  and  determined  on  a  course  of  dieting 
which  should  largely  reduce  the  protein  and  the  calorific  intake. 
The  rheumatic  trouble  disappeared,  and  minor  troubles,  such 
as  "sick  headaches"  and  "bilious  attacks,"  no  longer  recurred 
periodically  as  before.  "There  was  a  greater  appreciation  of 
such  food  as  was  eaten;  a  keener  appetite  and  more  acute  taste 
seemed  to  be  developed,  with  a  more  thorough  liking  for  simple 
foods."  During  the  first  eight  months  of  the  dieting  there  was 
a  loss  of  eight  kilograms  of  body  weight.  Thereafter  for  nine 
months  the  body  weight  remained  stationary.  "Two  months  of 
the  time  were  spent  at  an  inland  fishing  resort,  and  during  a 
part  of  this  time  a  guide  was  dispensed  with  and  the  boat  rowed 
by  the  writer  frequendy  six  to  ten  miles  in  a  forenoon,  some- 
times against  head  winds  (without  breakfast)  and  with  much 
greater  freedom  from  fatigue  and  muscular  soreness  than  in 
previous  years  on  a  fuller  dietary." 

During  the  period  of  nine  months  the  nitrogen  of  the  urine 
was  determined  daily.  The  average  was  5.69  grams.  During 
the  last  two  months  and  a  half,  the  average  elimination  was  5.40 
grams  for  a  body  weight  of  57.5  kilograms.  Experiments 
showed  that  about  one  gram  of  nitrogen  was  eliminated  in  the 
feces  and  that  nitrogen  equilibrium  could  be  maintained  with 
dietaries  of  low  calorific  values  (1613  and  1549  calories  =  28  and 
27  calories  per  kilogram)  containing  6.40  and  5.86  grams  of 

'  Chittenden:    "Physiological  Economy  in  Nutrition,"  1904. 


214  SCIENCE    OF   NUTRITION. 

nitrogen.  These  figures  correspond  to  diets  containing  40.0  to 
36.6  grams  of  protein  instead  of  the  118  grams  honored  by  habit 
and  tradition.  Professor  Chittenden  proclaims  such  a  diet  as  of 
the  highest  importance  to  health. 

The  case  of  Chittenden  recalls  a  note  from  an  early  convert 
to  the  "Graham  system"  of  vegetarianism.  Sylvester  Graham, 
in  1829,  began  the  advocacy  of  moderation  in  the  use  of  a  diet 
consisting  of  vegetables,  Graham  bread  (made  of  unbolted  flour), 
fruits,  nuts,  salt,  and  pure  water,  and  excluding  meat,  sauces, 
salads,  tea,  coffee,  alcohol,  pepper  and  mustard.  The  letter 
reads  as  follows:^  "The  first  three  months  of  my  experiment 
on  the  Graham  system  was  attended  by  a  loss  of  20  to  30  pounds 
of  flesh.  Some  of  my  neighbors  expostulated  with  me, — told 
me  I  should  destroy  myself  by  starvation,  and  it  was  even  re- 
ported in  a  neighboring  town  that  I  had  actually  died  from  that 
cause.  But  my  appetite  was  increasingly  good  and  my  health 
was  increasing,  and  in  a  short  time  my  headaches,  colds,  cos- 
tiveness,  and  rheumatism  left  me  entirely,  together  with  my 
hypochondriacal  and  gloomy  state  of  mind,  and  have  not  re- 
turned since,  notwithstanding  I  have  been  as  much  exposed 
to  wet  and  cold  as  at  any  period  of  my  life." 

Chittenden's  experiments  were  not  confined  to  an  indi- 
vidual nor  to  a  single  group  of  individuals.  Other  experi- 
ments were  made  on  professional  men,  on  student  athletes  in 
training,  and  on  soldiers  under  military  regime.  The  daily 
nitrogen  in  the  urine  in  periods  extending  from  five  to  nine 
months  averaged  as  shown  in  the  table  on  p.  215  in  the  indi- 
viduals belonging  to  the  three  groups. 

At  convenient  periods  during  the  experiments  it  was  deter- 
mined that  the  body  was  being  maintained  in  nitrogenous 
equilibrium  on  the  diet  which  gave  rise  to  the  stated  amounts 
of  urinary  nitrogen  (p.  182). 

The  professional  group  alleged  a  greater  keenness  for  its 

^  Charles  Clapp:  "The  Graham  Journal  of  Health  and  Longevity,"  Boston, 
1837,  vol.  i,  p.  57. 


A    NORMAL    DIET. 


215 


work,  the  athletic  group  won  championships  in  games,  and  the 
soldiers  maintained  perfect  health  and  strength,  many  professing 
repugnance  to  meat  w^hen  they  were  allowed  it  after  five  months 
of  practical  abstinence. 


Professors  and  Teachers. 

University  Athletes. 

1     United  States  Soldiers. 

Weight  in  Kg. 

1 

N  in        1 
Urine  in  G.  | 

Weight  in  Kg. 

N  in 
Urine  in  G. 

1   Weight  in  Kg. 

N  in 
Urine  in  G. 

1 

71° 

61.0 

78.0 

83-0 

62.0 

.  56-0 

73-0 

7S-0 

9-37 

10.41 

8.88 

9.04 

7-47 

7-58 

10.09 

11.06 

62 

7.42 
7.0^ 

6-53       1 

59 

60 

7.26 
8.17 
8.39 
7-13 
8.91 
7.84 
8.05 
7-38 
8.25 
8.08 
8.61 

c8 

61  :; 

8.58 

60 

c  ?                 

1 

162 

1 

59 

55 

65 

57 

Although  it  is  possible  that  the  alleged  improved  mental 
condition^  may  have  been  due  to  suggestion  (p.  302),  still  the 
fact  remains  that  it  has  been  proved  by  Chittenden's  work 
that  the  allowance  of  protein  necessary  for  continued  health  and 
strength  may  be  reduced  during  many  months  to  half  or  less  of 
what  the  habit  of  the  appetite  suggests. 

It  remains  to  be  seen  whether  this  quantity  of  protein  in 
the  ration,  which  is  not  greater  than  the  body  would  metabolize 
in  starvation,  is  advisable  as  a  program  for  the  whole  of  one's 
adult  life. 

The  foods  with  the  strongest  flavors  are  meats,  which  there- 
fore add  relish  to  a  repast,  and  stimulate  the  digestive  secretions. 

Chittenden  believes  that  the  large  quantity  of  protein  in  an 
ordinary  diet  is  due  to  self-indulgence.  He  protests  against  such 
indulgence,  and  thinks  that  a  needless  strain  is  thereby  imposed 


•  Chittenden:   Loc.  cit.,  p.  51. 


2i6  SCIENCE   OF  NUTRITION. 

upon  the  liver,  the  kidneys,  and  other  organs  concerned  in  the 
transformation  and  ehmination  of  the  end-products  of  protein 
metabohsm. 

Lichtenfelt,^  on  the  other  hand,  shows  that  while  there  is  no 
statistical  difference  in  the  height  of  individuals  as  due  to  oc- 
cupation, still  the  people  of  southern  Italy  are  not  so  large  nor 
so  well  developed  physically  as  their  fellows  of  northern  Italy. 
He  explains  this  stunted  growth  as  due  to  a  low  protein  and  cal- 
orific intake  in  the  food. 

Hirschfeld^  finds  that  the  actual  ration  of  a  German  soldier 
contains  98  grams  of  protein,  with  no  untoward  results.  He 
states  that  writers  on  economics,  who  believe  the  German  popu- 
lace underfed  because  they  do  not  have  118  grams  of  protein 
daily,  are  unduly  pessimistic. 

Although,  as  has  been  stated,  the  battle-ground  has  been 
over  the  allowance  of  118  grams  in  Voit's  dietary,  it  will  be  sur- 
prising to  many  to  learn  that  Voit  himself  said  little  on  the 
subject.  He^  showed  that  a  vegetarian  can  live  in  nitrogenous 
equilibrium  on  a  diet  containing  48.5  grams  of  protein  and 
that  an  active  working  man  weighing  74  kilos  may  get  along 
on  less  than  118  grams.  He  discouraged  the  tendency  to  eat 
meat  in  excess.  He  also  discouraged  the  practice  of  vegetarians 
who  overload  the  digestive  tract  with  the  coarser  kinds  of  vege- 
table foods  which  leave  large  indigestible  residues. 

It  is  not  to  be  denied  that  50  grams  of  protein  (containing 
8  grams  of  nitrogen)  are  apparently  able  to  maintain  the  adult 
body  machine  in  perfect  repair.  Vegetarians,  fruitarians*  (who 
live  on  fruit  and  nuts),  and  vigorous  adults  who  largely  exclude 
protein  from  the  diet,  are  evidently  able  to  live  in  health  and 
strength  upon  this  quantity.  It  must  be,  however,  that  more 
than  this  amount  is  advisable  during  growth  or  convalescence 

^Lichtenfelt:   "Pfliiger's  Archiv,"  1905,  Bd.  cvii,  p.  57. 
^  Hirschf eld :   "Archiv  fiir  Physiologie,"  1900,  p.  380. 
^  Voit:   "Zeitschrift  fiir  Biologic,"  1889,  Bd.  xxv,  p.  278. 
*  Jaffa:  U.  S.  Department  of  Agriculture,  Bulletin  No.  132. 


A   NORMAL    DIET. 


217 


from   wasting   disease,    or   during   the   muscular   hypertrophy 
which  accompanies  preliminary  training  for  athletic  effort. 

Abderhalden^  mentions  the  fact  that  since  various  body 
tissues  are  constructed  of  different  proteins,  therefore  a  large 
variety  of  amino-acids  in  sufficient  quantity  must  be  available 
for  their  proper  replenishment.  Hence,  it  is  reasonable  to 
assume  that  a  considerable  excess  of  food  protein  is  essential 
to  supply  the  special  amino-products  for  the  synthesis  of  the 
characteristic  proteins  of  the  blood  serum  and  those  of  the 
different  organs. 

It  is  certain  that  large  ingestion  of  protein  in  hot  weather 
increases  the  heat  production  with  accompanying  increase  in 
perspiration  (p.  154).  Meat  should  therefore  be  avoided  in 
hot  weather.  In  cold  weather  such  an  extra  heat  production 
may  produce  a  pleasurable  sensation  of  warmth.  Dr.  Folin,  in 
personal  conversation  with  the  wTiter,  said  that  a  dietary  of 
carbohydrates,  fat,  and  low  protein,  was  easily  borne  by  an 
individual  during  the  summer,  but  during  the  winter  the  man 
complained  of  his  sensitiveness  to  cold  when  taking  the  same 
diet. 

Ranke^  describes  experiments  on  himself  (weight  =  73 
kilograms)  during  the  hottest  months  of  summer  weather  in 
Munich,  at  which  time  he  partook  of  an  ample  diet,  rich  in  pro- 
tein (135  grams),  containing  3300  calories, — a  diet  which  he  ■ 
had  enjoyed  during  the  preceding  winter.  He  had  to  force 
himself  to  eat.  He  was  first  attacked  by  catarrh  of  the  stomach, 
from  which  he  recovered  by  dieting,  and  subsequently  became 
infected  by  diphtheria.  He  had  formerly  suffered  from  catarrh 
of  the  stomach  while  residing  in  the  tropics.  The  excess  of  food, 
and  especially  of  protein,  threw  an  unnecessary  burden  upon 
the  heat-regulating  apparatus  which  would  not  have  taken  place 
had  the  dictates  of  the  appetite  been  allowed  full  sway  and  had 
the  ration  voluntarily  been  reduced. 

'  AfxJcrhalden:    "Zenlralblatt  fiir  d.  gcs.  Physiol,  und  Path.  d.  SloiTwcch- 
sels,"  1906,  Bd.  i,  p.  225. 

*Ranke:   "Zcitschrift  fur  Biologic,"  1900,  Bd.  xl,  p.  299. 


21 8  SCIENCE    OF   NUTRITION. 

From  the  knowledge  at  hand  there  appears  to  be  no  strongly 
substantiated  argument  why  that  portion  of  mankind  living  in 
a  cool  climate  should  not  follow  the  general  custom  of  taking  a 
medium  amount  of  protein  in  moderate  accordance  with  the 
dictates  of  their  appetites.  Everyone  knows  that  excessive 
ingestion  of  highly  flavored  meats  results  in  jaded  appetite,  an 
automatic  signal  of  excess. 

A  similar  excess  of  food  when  given  to  dogs  results  in  vomit- 
ing. Rubner^  says  that  many  years  of  experience  with  dogs 
leads  him  to  believe  that  appetite  and  capacity  for  digestion  and 
absorption  depend  on  the  dog's  requirement  for  energy  in  his 
given  state  of  nutrition.  A  diet  which  a  dog  will  greedily  devour 
when  in  a  room  at  a  temperature  of  o°,  he  will  in  part  refuse 
when  at  a  temperature  of  33°. 

While  the  protein  quantity  in  the  diet  may  vary  within 
wide  limits  with  the  taste,  the  purse,  or  the  fad  of  the  individual, 
the  quantity  of  energy  required  by  the  organism  is  a  remark- 
ably constant  factor,  being  35  calories  per  kilogram  of  body 
weight  in  the  average  man  doing  light  work  on  a  mixed  diet. 
Comparatively  little  of  this  energy  is  furnished  by  protein. 

In  a  fasting  individual,  protein  furnishes  13  and  fat  87  per 
cent,  of  the  total  heat  given  off  from  the  body. 

In  Voit's  medium  mixed  diet  designed  for  a  laboring  man, 
the  118  grams  of  protein  furnish  about  15  per  cent,  of  the  total 
of  3055  calories. 

In  such  an  experiment  as  Siven's,  mentioned  on  page  212, 
which  represents  the  lowest  possible  level  of  nitrogen  equilibrium, 
the  25  grams  of  protein  ingested  furnished  100  calories  out  of 
2717  ingested  in  the  food,  or  3.6  per  cent.  However,  since  the 
total  metabolism  was  measured  as  2082  calories,  the  protein 
furnished  approximately  5  per  cent,  of  this  energy. 

Chittenden^  gives  a  dietary  containing  50  grams  of  protein 
and  2500  calories  as  sufficient  for  a  soldier  at  work.     This 

^  Rubner:   "  Energiegesetze,"  1902,  p.  83. 
^Chittenden:  Loc.  cii.,  p.  254. 


A   NORMAL    DIET.  21 9 

allows  8  per  cent,  of  the  total  energy  in  protein.     These  data 
may  be  thus  summarized: 

Cal.  from  Pro-  Cal.  from  Fat  and 
Grams  of        tein  Metabo-        Carbohydratf, 
Protein               lism  in  Metabolism  in 

IN  Diet.  per  cent.  per  cent. 

Starvation o  13  87 

Voit's  standard  (liberal  protein)  .  118  15  85 
Chittenden's  standard  (reduced 

protein) 50  S  92 

Siven's  minimum 25  5  95 

The  energy  other  than  that  contained  in  protein  may  be 
given  as  carbohydrates  or  as  fat.  Voit  allows  a  laborer  500 
grams  of  starch  (2050  calories)  as  the  quantity  which  the  in- 
testinal canal  may  readily  digest,  and  adds  56  grams  of  fat  (521 
calories)  to  the  diet. 

It  has  already  been  observed  that  half  the  energy  may  be 
given  in  fat  and  half  in  carbohydrates  without  affecting  the 
carbohydrate  power  of  economy  over  the  protein  metabolism 
(p.  181V 

This  part  of  the  subject  really  becomes  a  mere  matter  of 
calculation  of  the  requirement  of  the  resting  organism,  and  the 
addition  thereto  of  sufficient  energy  to  accomplish  the  mechani- 
cal work. 

How  this  is  done  has  already  been  set  forth  in  another  chap- 
ter. A  bicyclist  riding  for  sixteen  hours  may  have  a  metabolism 
amounting  to  9000  calories  daily,  and  the  average  ration  of  a" 
Maine  lumberman  may  rise  to  a  value  of  8000  calories.  Cham- 
pion wresders  in  a  world's  contest^  may  ingest  daily  during  their 
periods  of  effort  diets  containing  protein  217.9  grams  (35.1  grams 
of  N);  fat,  259.5  grams;  carbohydrates,  431  grams;  together, 
5070  calories:  or  protein,  182.2  grams  (29.2  grams  N);  fat,  204.6 
grams;  carbohydrates,  392.3  grams;  together,  4254  calories. 
Much  cream  was  taken  by  these  last-named  individuals. 

Chittenden^  has  fallen  into  error  in  the  commendation  of 
2500  to  2600  calories  as  an  ample  diet  for  a  soldier  at  drill. 

'Lavonius:    "Skan.  Archiv  fur  Physiologic,"  1905,  Bd.  xvii,  p.  196. 
*  Chittenden:    Loc.  cit.,  p.  254. 


220  SCIENCE   OE   ZSTUTRITION. 

For  himself,  pursuing  a  sedentary  life,  Chittenden  prescribes 
2000  calories  or  35  per  kilogram,  while  Mendel  requires  2448 
calories,  or  35.3  calories  per  kilogram.  These  are  entirely- 
normal  values  for  people  at  light  work.  In  the  earliest  calcula- 
tions of  Voit,  in  1866,  it  was  shown  that  a  man  of  70  kilograms 
on  a  medium  mixed  diet,  produced  2400  calories,  or  34.3  calories 
per  kilogram;  and  Rubner  allows  2445  calories  to  men  of  70 
kilograms  weight  engaged  in  occupations  involving  light  mus- 
cular work, — such  men  as  writers,  draughtsmen,  tailors,  phy- 
sicians, etc.  But  the  soldiers  under  Chittenden  were  put  for 
two  hours  in  the  gymnasium,  then  apparently  drilled  for  one 
hour,  and  walked  another  hour.  This  physical  work  requires 
increased  energy  from  metabolism.  It  has  been  shown  that  to 
walk  2.7  miles  in  an  hour  on  a  level  road  requires  an  increased 
metabolism  of  159.2  calories  in  a  man  weighing  70  kilograms. 
If  a  soldier  during  four  hours  actually  expended  this  equivalent 
mechanical  energy  in  excess  of  the  amount  of  Professor  Mendel 
in  his  laboratory,  then  his  metabolism  would  be  larger  than 
Professor  Mendel's  by  637  calories,  or  he  would  have  a  total 
metabolism  of  3085. 

In  Chittenden's  experiments  there  was  no  analysis  of  the 
expired  air,  and  conclusions  are  drawn  from  the  maintenance 
of  body  weight. 

Several  of  the  larger  sized  soldiers  (those  who  weighed  70 
kilograms)  lost  between  3.5  and  8.5  kilograms  of  body  weight 
during  the  experiments.  Fritz,  weighing  76.0  kilograms,  lost 
3.6  kilograms  in  five  months.  Had  this  all  been  fat,  one  can 
estimate  that  its  heat  value  would  have  been  33,480  calories, 
or  an  available  daily  combustion  of  body  substance  equal  to 
223  calories.  Conclusions  drawn  from  weight  alone  can  be  of 
only  the  roughest  character  (see  p.  73). 

For  ordinary  laborers  working  eight  to  ten  hours  a  day — 
such  as  mechanics,  porters,  joiners,  soldiers  in  garrison,  and 
farmers^3ooo  calories  does  not  seem  an  excessive  quantity. 

Rubner's  diet  calls  for  2868  calories.     Chittenden's  allow- 


A   NORMAL    DIET.  221 

ance  (2500-2600)  is  too  low,  while  Atwater's  (3400)  appears 
excessive. 

A  third  class  are  men  at  hard  labor,  such  as  soldiers  in  the 
field,  shoemakers,  blacksmiths,  etc.  For  these  Voit  allows  a 
dietary  containmg  3574  calories;  Rubner  3362  calories;  and 
Atwater  4150  calories.  The  differences  in  these  figures  are 
merely  differences  in  the  quantity  of  work  alone. 

In  almost  all  the  rations  given,  carbohydrates  do  not  exceed 
500  grams.     The  remainder  is  made  up  of  fat. 

Atwater^  reports  the  following  dietaries  for  farmers: 

Calories. 

Farmers  in  Connecticut 3410 

"  "  Vermont 3635 

"         "  New  York 3785 

"  Mexico 3435 

"  Italy 3565 

To  this  list  may  be  added  for  farmers  in  Finland  3474  calories 
as  found  in  the  exhaustive  studies  of  Sundstrom.^  Sundstrom 
states  that  the  diet  of  the  average  Finnish  peasant  contains  136 
grams  of  protein,  83  grams  of  fat,  and  580  grams  of  carbohy- 
drates, which  corresponds  to  a  division  of  calories  so  that  pro- 
tein furnishes  15  per  cent.,  fat  21  per  cent.,  and  carbohydrates 
64  per  cent,  of  the  total.  He  notes  that  if  the  peasant's  re- 
quirement of  energy  were  taken  in  rye  bread  alone  124 
grams  of  protein  would  be  ingested  with  it,  whereas  if  a  milk 
diet  covered  the  requirement  195  grams  of  protein  would  be- 
taken. He  therefore  sees  no  outlook  for  a  low  protein  dietary 
among  the  poorer  classes. 

Woods  and  Mansfield''  report  a  dietary  study  of  a  camp  of 
fifty  Maine  lumbermen  actively  engaged  in  chopping  and  yard- 
ing logs.  The  investigation  continued  for  six  days.  The  daily 
average  ration  per  man  was  as  follows:  Protein,  164.1  grams; 
fat,  387.8  grams,  carbohydrates,  982.0  grams;  calories,  8083.0. 
This  dietary  would  appear  almost  fabulous  were  it  not  for 

'Atwater:     Report  of  Storr's  Agricultural  .Station,  1902-03,  p.  135. 
'.Sundstrom:     Untersuchungen  uber  <Jie  Krnalirung  der   Landhcvolkcrung 
in  Finland,  1908.  •*  Woods  and  Mansfield :   Loc.  cil. 


222 


SCIENCE    OF   NUTRITION. 


the  fact  that  Atwater  has  actually  shown  that  a  metabolism 
equivalent  to  9300  calories  a  day  may  be  produced  by  a  man 
riding  a  stationary  bicycle  for  sixteen  hours. 

A  lower  ration  than  the  lowest  here  mentioned  may  be 
allowed  to  one  who  is  confined  to  his  bed  (p.  82).  In  many 
hospitals,  however,  it  has  been  found  that  liberal  feeding  of 
the  very  poor  is  often  better  than  medicine. 

The  "standard"  dietaries  are  given  below,  not  because  they 
are  inflexible  requirements  in  any  sense  of  the  word,  but  merely 
for  the  convenience  of  the  reader.  The  individual  standard 
will  ever  be  controlled  by  climate,  the  amount  and  kind  of 
mechanical  effort;  by  appetite,  purse  and  dietetic  prejudice. 

STANDARD    DIETARIES    FOR   A    MAN    OF    70    KILOGRAMS. 
(Weights  in  Grams.) 

VOIT. 

Light  work: 

Protein 

Fat 

Carbohydrates 

Calories 

Medium  work: 

Protein ii8 

Fat 56 

Carbohydrates 500 

Calories 3055 

Hard  work: 

Protein 145 

Fat 100 

Carbohydrates 500 

Calories 3574 

*  Carbohydrates  and  fats  to  make  up  the  fuel  value. 

Rubner^  cites  the  following  food  values  consumed  daily  per 
inhabitant  of  different  cities,  based  upon  municipal  statistics  of 
gross  consumption: 

MUNICIPAL  FOOD  STATISTICS. 


RUBNER. 

Atwater 

123 

100 

46 

* 

377 

* 

2445 

2700 

127 

52 

509 
2868 

125 
* 

* 

3400 

165 

70 

565 
3362 

150 
* 
* 

4150 

HPI' 

Protein. 
(Grams.) 

Fat. 
(Grams.) 

Carbohydrates. 
(Grams.) 

Calortes. 

84 
96 
98 
98 

31 

65 
64 
60 

414 
492 

465 
416 

2394 
30T4 
2903 
2665 

Munich 

Paris 

London 

^Rubner:  Von  Leyden's  "Handbuch  der  Ernahrung,"  1903,  Bd.  i,  p.  160. 


A   NORMAL    DIET. 


223 


In  contrast  to  this  comparative  uniformity  hospital  dietaries, 
as  regulated  by  the  management  of  such  institutions,  vary  greatly. 
Rubner^  cites  the  following  hospital  dietaries: 


HOSPITAL  DIETARIES. 


Munich. . 
Augsburg 

HaUe 

England. 


Protein. 

Fat. 

(Grams.) 

(Grams.) 

92 

54 

94 

57 

92 

30 

107 

69 

Carbohydrates. 

(Grams.) 


157 
222 

393 
533 


Calories. 


1823 
2267 
3266 


The  population  of  a  city  will  ordinarily  sustain  itself  in 
accordance  with  its  needs.  In  public  institutions,  however, 
such  as  poorhouses,  prisons,  asylums,  hospitals,  and  in  militar\' 
and  naval  establishments,  scientific  knowledge  of  the  needs  of 
the  individual  becomes  a  very  important  consideration.  The 
prolonged  endurance  of  an  army  of  soldiers  is  just  as  dependent 
on  an  ample  army  ration  as  is  the  battleship  dependent  on  its 
supply  of  fuel.  Not  only  the  quantity  of  the  food  makes  for  the 
well-being,  but  it  must  taste  well.  No  amount  of  actual  fuel 
value  could  compel  the  American  soldiers  of  the  Spanish- 
American  war  to  eat  the  "embalmed  beef"  furnished  by  the 
Government.  The  flavor  is  to  the  man  what  oil  is  to  the  ma- 
chinery of  the  battleship.  Without  flavor  in  the  food  the  diges- 
tive apparatus  does  not  run  smoothly.  In  ordinary  ci\'ilized 
life  even  psychical  influences  act.  The  cloth  on  the  table  must 
be  spotless,  and  the  environment  inviting. 

One  takes  as  food  milk,  eggs,  various  meats,  such  as  beef, 
veal,  pork,  mutton,  fish;  also  cereals,  such  as  bread,  rice,  corn, 
macaroni,  beans,  and  peas.  Sometimes  alcoholic  beverages  are 
added.  The  calorific  values  of  the  various  nutrient  materials 
may  be  calculated  by  determining  the  composition  of  the  latter 
by  analysis  and  by  multiplying  the  number  of  grams  of  each 

'  Rubner:   Loc.  cit.,  p.  157. 


224  SCIENCE    OF   NUTRITION. 

constituent  by  the  factor  which  represents  its  fuel  value  to  the  or- 
ganism (p.  41). 

As  a  simple  illustration  of  this  the  following  experiment  of 
Rubner^  may  be  cited.  A  man  weighing  46  kilograms  ate 
nothing  but  eggs  for  two  days, — 22  on  the  first  day  and  20  on 
the  second.  The  22  eggs  contained  1017.4  grams  of  material; 
the  20,  878.8  grams;  an  average  of  948.1  grams  per  day.  Since 
100  grams  of  egg  contain  14.1  grams  of  protein  and  10.9  grams 
of  fat,  948.1  grams  would  contain  a  daily  allowance  of  133.6 
grams  of  protein  and  103  grams  of  fat.  If  Rubner's  standard 
values  for  the  energy  content  are  used,  the  result  will  be  as  fol- 
lows: 

133.6  grams  protein  X  4.1  =     547  calories. 
103.3  graras  fat  X  9-3  =     967  calories. 

Total =  15 14  calories. 

or  33  calories  per  kilogram. 

This  dietary  of  eggs  was  therefore  nearly  sufficient  for  the 
fuel  requirement  of  this  undersized  individual.  Notwithstand- 
ing the  large  amount  of  protein  in  the  dietary,  there  was  a  loss 
of  body  protein  equal  to  7.5  grams  per  day. 

The  results  of  an  exclusive  milk  diet  are  thus  summarized  by 
Rubner:^  Milk  (2438  grams)  containing  84  grams  of  protein  and 
two-thirds  of  the  requirement  of  energy  for  the  individual,  pro- 
duced a  deposit  of  protein  equal  to  6.7  grams  daily  (p.  182).  To 
cover  a  requirement  of  2400  calories  daily  3410  grams  of  milk 
would  be  needed,  which  contain  140  grams  of  protein.  For 
a  laboring  man  with  a  requirement  of  3080  calories,  4380  grams 
of  milk  with  180  grams  of  protein  would  be  necessary. 

It  is  evident  that  milk  with  its  high  protein  content  is  a  food 
par  excellence  for  the  growing  organism  or  for  the  invalid  conva- 
lescing from  wasting  disease.  It  contains  too  large  an  amount 
of  protein  for  a  normal  adult.     A  mixture  of  milk,  toast,  and 

^Rubner:    "Zeitschrift  ftir  Biologie,"  1879,  Bd.  xv,  p.  127. 
^Rubner:    Von  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1903,  Bd. 
i,  p.  132. 


A    NORMAL   DIET. 


225 


cream  (creamed  milk-toast)  may  produce  a  modified  milk  diet  of 
proper  value  and  easy  digestibility.  An  exclusive  milk  diet  con- 
tains too  little  iron  for  the  needs  of  a  normal  adult. 

Moritz^  recommends  milk  alone  in  treatment  of  obesity, 
in  quantities  varying  between  1.5  and  2.5  liters  daily.  The 
normal  weight  in  kilograms  of  the  individual  is  calculated  from 
his  height,  and  each  kilogram  of  such  weight  is  provided  with 
16  to  17  calories  in  the  diet,  an  amount  which  is  contained  in 
25  c.c.  of  milk.  Should  the  normal  weight  be  80  kilograms, 
2000  grams  of  milk  are  administered  daily  in  five  portions. 
Such  treatment  brings  about  a  considerable  loss  in  body  weight, 
and,  although  some  body  nitrogen  is  lost,  a  state  of  weakness 
does  not  ensue. 

Rubner  finds  that  1500  grams  of  good  white  bread  contain- 
ing 104.4  grams  of  protein  (  =  75.2  grams  pure  protein)  will 
maintain  a  working  man  in  nitrogenous  and  calorific  equilibrium. 

Atwater  and  Benedict^  have  conclusively  shown  that  alcohol 
may  be  used  in  the  economy  in  place  of  isodynamic  quantities  of 
carbohydrates  and  fats.  The  following  table  shows  the  average 
of  experiments  on  a  resting  individual  which  lasted  twenty-three 
days: 

INFLUENCE  OF  ALCOHOL  ON  METABOLISM. 


D0RA- 

TION  IN 

Days. 

In  the  Food  in  Grams. 

Alco- 
hol. 

Cal.  in 
Food. 

Cal.  of 
Metabo- 
lism. 

Protein 
Balance. 

Protein. 

Fat. 

Carbo- 
hydrates 

Ordinary  diet. . 
Alcohol  contain- 
ing diet 

13 
10 

114 
"5 

69 
47 

354 
273 

72.2 

2496 

2488 

2221 

2221 

— 2.0 
-3-8 

Atwater  and  Benedict    employed    diets   containing  about 
2500  calories  for  a  man  at  rest  and  3500  for  a  man  at  work. 


'Moritz:    "  Miinchener  mcdizinische  Wochenschrift,"  1908,  July,  No.  30. 
*  Atwater  and  Benedict:   "Memoirs  of  the  National  Academy  of  Sciences," 
Washington,  1902,  vol.  viii,  p.  231. 

15 


226  SCIENCE   OF   NUTRITION. 

During  the  alcohol  days  500  of  the  calories  were  supplied  in 
72  grams  of  alcohol,  or  about  what  is  contained  in  a  bottle 
of  claret.  The  metabolism  of  the  individual  as  expressed  in 
calories  was  unchanged  by  the  addition  of  alcohol  to  the  diet. 
The  alcohol  was  given  in  six  small  doses  and  98  per  cent,  was 
burned  by  the  organism. 

On  the  ordinary  diet  33.7  grams  of  fat  were  daily  added  to 
the  body,  and  on  the  alcohol  days  34.1  grams.  These  very 
valuable  observations  make  it  evident  that  alcohol  is  not  a  direct 
cause  of  obesity.  If,  however,  a  young  man  having  acquired 
certain  dietary  habits  at  home,  continues  the  same  diet 
at  college  and  begins  to  drink  "in  moderation"  besides,  his 
increasing  rotundity  as  he  returns  on  his  vacations  can  be  readily 
explained  by  the  sparing  influence  of  alcohol  upon  the  fat  in 
his  diet. 

A  liter  of  German  beer  contains  3  to  4  per  cent,  of  alcohol 
and  5  to  6  per  cent,  extractives.  It  yields  450  calories  to  the 
body,  only  half  being  derived  from  alcohol,  the  rest  from  the 
dextrin  and  protein-like  extractives.  Here  is  a  material  whose 
"fattening"  properties  may  be  very  highly  considered. 

AU  alcoholic  beverages  are  taken  with  a  twofold  object, — 
first,  the  desire  for  flavor,  and  second,  for  stimulation.  Their 
food  value,  as  above  described,  is  usually  little  considered.  In 
general  it  maybe  said  that  alcohol  as  a  stomachic  is  valueless- 
when  the  gastric  juice  is  normal,  but  is  beneficial  in  cases  of 
supersecretion,  hypochlorhydria,  and  loss  of  appetite.  Under 
these  circumstances  smaU  amounts  of  beverages  containing  5  to 
ID  per  cent,  of  alcohol  are  sufficient  for  all  purposes.^ 

In  the  light  of  the  social  evils  which  accompany  the  exces- 
sive use  of  alcohol  as  a  beverage  there  is  no  doubt  that  its  total 
prohibition — if  this  were  possible — would  make  for  the  public 
weal  and  improve  the  physical  and  moral  condition  of  mankind. 

The  subject  of  alcohol  could  be  spun  out  into  a  considerable 

^Zitowitsch:  Abstract  in  "Biochem.  Centralblatt,"  1905,  Bd.  iv,  p.  574. 


A   NORMAL   DIET.  227 

story,  but  for  further  details  the  reader  is  referred  to  other 
sources/ 

To  arrange  a  proper  dietary  for  a  given  individual  or  group 
of  individuals  the  very  complete  and  valuable  tables  of  Atwater 
will  be  found  most  practical.  They  are  placed  in  an  appendix 
at  the  end  of  this  volume  for  the  benefit  of  the  student  who  may 
desire  to  apply  in  practice  his  knowledge  of  the  general  laws 
of  metabolism. 

Underfed  or  overfed  individuals  may  alike  become  objects 
of  commiseration  and  proper  subjects  for  rehabilitation. 

^The  Use  of  Alcohol  in  Medicine:  F.  G.  Benedict,  A.  R.  Cushny,  S.  J. 
Meltzer,  Graham  Lusk,  "Boston  Medical  and  Surgical  Journal,"  1902,  vol. 
cxlvii,  p.  31;  Bibliographie  der  gesammten  wissenschaftlichen  Literatur  liber 
den  Alkohol  und  den  Altoholismus,  1904,  by  Emil  Abderhalden. 


CHAPTER  X. 

THE  FOOD  REQUIREMENT  DURING  THE  PERIOD 
OF  GROWTH. 

"Mute  and  still,  by  night  and  by  day,  labor  goes  on  in  the 
workshops  of  life.  Here  an  animal  grows,  there  a  plant.  The 
wonder  of  the  work  is  not  less  in  the  smallest  being  than  in 
the  largest."  ^ 

In  the  last  chapter  the  average  food  requirement  of  a  normal 
adult  organism  was  discussed.  This  diet,  however,  may  be 
exceeded  in  cases  where  there  is  a  renewal  of  tissue  following 
wasting  disease,  or  where  there  is  a  development  of  new  tissue, 
as  during  pregnancy,  or  afterwards  during  lactation,  which  in- 
volves the  growth  of  the  new-born  infant. 

TangP  has  reported  some  interesting  observations  on  the 
heat  production  which  takes  place  in  the  hen's  egg  incubated 
at  38°  and  39°.  Tangl  called  this  the  "energy  for  development" 
or  the  "ontogenetic  energy."  His  method  was  to  determine 
the  calories  in  fresh  laid  eggs  and  to  compare  that  amount  with 
the  calories  found  within  the  egg-shell  at  the  moment  of  the 
birth  of  the  chick.  In  this  latter  case  the  chick  and  the  balance 
of  egg-yolk  were  determined  separately. 

The  results  of  these  experiments  showed  that  for  the  devel- 
opment of  one  gram  of  chick  658  small  calories  were  used,  or 
for  the  production  of  one  gram  of  solids  contained  in  a  new- 
born chick  3425  small  calories  were  required. 

Farkas^  has  since  shown  that  for  the  development  from  the 

^Rubner:  "  Verhandlungen  der  Ges.  der  Naturforscher  und  Arzte,"  1908, 

P-  77- 

^Tangl:  "Pfliiger's  Archiv,"  1903,  Bd.  xciii,  p.  327. 
^Farkas:  Ihid.,  Bd.  xcviii,  p.  490. 

228 


FOOD    REQUIREMENT   DURING   GROWTH.  220 

egg  of  one  gram  of  silkworm  larvs  882  small  calories  are  re- 
quired, or  for  one  gram  of  dry  solids,  3125  small  calories, 
figures  which  he  compares  with  Tangl's  for  the  egg. 

When  the  whole  hen's  egg  is  considered,  Tangl  finds  that 
32  calories  or  35  per  cent,  of  the  amount  of  chemical  energy  in 
the  original  egg  is  deposited  in  the  body  of  the  young  embryo. 
The  energy  of  development  used  in  the  production  of  the  young 
chick  amounts  to  sixteen  calories  or  17  per  cent,  of  the  original 
total.  The  balance  or  48  per  cent,  of  the  original  energy 
in  the  egg  is  largely  found  in  the  abdomen  of  the  chick  and  is  ab- 
sorbed by  the  animal  during  the  early  days  of  life. 

It  is  apparent  from  the  above  that  approximately  one- sixth  of 
the  energy  in  a  hen's  egg  is  used  in  the  development  of  a  chick 
whose  body  contains  one-third  the  original  energy  of  the  ego-. 
The  other  half  of  the  energy  becomes  available  for  the  chick 
during  the  first  days  of  its  life,  through  absorption  from  the 
intestinal  wall. 

Tangl  finds  that  each  egg  loses  in  solids  during  incubation, 
and  that  the  heat  value  of  one  gram  of  such  solids  is  over  9 
calories.  Since  one  gram  of  fat  yields  9.3  calories,  the  natural 
inference  is  that  fat  furnishes  the  energy  for  development. 

Hasselbalch^  had  formerly  shown  that  the  respiration  carried 
on  by  an  egg  indicated  a  respiratory  quotient  (^')  amounting 
to  0.677.     This  low  quotient  points  to  the  combustion  of  fat. 

TangP  also  states  that  there  is  no  loss  of  protein  nitrogen 
by  the  egg  during  incubation,  and  that  the  egg-shell  contributes 
to  bone  formation  in  the  chick. 

It  is  obvious  from  this  work  that  chemical  energy  derived 
principally  from  the  oxidation  of  fat  is  used  in  the  development 
of  the  embr>'onic  chick — the  energy  of  ontogenesis.  So,  during 
pregnancy  in  the  higher  animals,  not  only  must  there  be  growth 
of  the  breasts,  .the  uterine  musculature,  and  growth  of  the 

'  Hassclbalch:   "Skan.  Archiv  fur  Physiol.,"  1900,  Bd.  x,  p.  353. 

'Tangl  and  Mituch:  "Pflugcr's  Archiv,"  1908,  Bd.  cxxi,  p.  437;  Tangl: 
Ibid.,  p.  423. 


230  SCIENCE   OF  NUTRITION. 

embryo  itself,  but  there  must  be  energy  expended  in  maintaining 
the  new  organism.  Hence  the  appetite  of  the  mother  increases 
during  pregnancy.  Magnus-Levy^  finds  an  increased  require- 
ment for  oxygen  on  the  part  of  the  mother  as  pregnancy  pro- 
gresses.    His  table  is  as  follows : 

Oxygen  in  c.c. 

PER   MIN. 

Non-pregnant 302 

Third  month  of  pregnancy 320 

Fourth     "  "         325 

Fifth        "  "         340 

Sixth        "  "         349 

Seventh    "  "         378 

Eighth     "  "         363 

Ninth      "  "         383 

Magnus-Levy  estimates  that  of  the  80  c.c.  additional  oxygen 
required  during  the  ninth  month  of  pregnancy,  only  10  c.c.  are 
used  for  the  metabolism  of  the  fetus,  20  c.c.  for  the  increased 
respiratory  and  heart  activity,  while  50  c.c.  are  for  the  general 
needs  of  the  maternal  organism,  which  has  increased  in  size 
and  weight. 

On  empirical  grounds  von  WinckeP  for  many  years  has 
used  the  following  diet  for  pregnant  women  with,  he  says, 
"  excellent  results  " : 

Protein 90  grams.  ^^Sg'calories. 

Fat 27     "  251       " 

Carbohydrates 200     "  820       " 

Total 1440       " 

This  certainly  seems  a  very  low  ration  and  one  hardly  com- 
patible with  furnishing  the  full  calorific  requirement.  It  may, 
however,  prevent  an  excessive  growth  of  the  child  within  the 
uterus. 

Murlin^  has  made  experiments  on  the  total  metabolism  in 

'Magnus-Levy:  " Zeitschrif t  f iir  Gynakologie  u.  Geburtshilfe,"  1904,  Bd. 
lii.  Also  see  Magnus-Levy:  Von  Noorden's  "Handbuch  des  Stoffwechsels," 
1906,  Bd.  i,  p.  409. 

^  Von  Winckel:  Von  Leyden's  "Handbuch  der  Emahrungstherapie,"  1904, 
Bd.  ii,  p.  469. 

^  Murlin:  Proceedings  of  the  American  Physiological  Society,  American 
Journal  of  Physiology,  1909,  vol.  xxiii,  p.  xxxii. 


FOOD   REQUIREMENT  DURING   GROWTH. 


231 


pregnant  dogs.  From  one  animal  a  single  puppy  was  bom  as 
the  result  of  a  first  pregnancy  and  a  litter  of  five  from  a  later  one. 
The  following  results  were  obtained : 


Day  from 

Date. 

Excreta. 

Calorfes 
OF  Meta- 
bolism. 

Parturition. 

Total  N. 

Total  C. 

Third  before 

First  after 

Nineteenth  after   . 

Third  before    

First  after 

June  23 
June  27 

July  IS 
Dec.  II 
Dec.  15 

8.6 

84 
5-3 
6.8 

8.3 

59-4 
65.8 
51-6 
74.7 
100.6 

551-3 
640.6 

505-3 

764.9 

1058.8 

/  One   puppy  born. 
\  Weight,  280 grams. 

Sexual  rest. 
/  Five  puppies  born . 
\  Weight,  1560  gms. 

The  increase  of  metabolism  which  can  be  attributed  to  the 
pregnant  condition  may  be  found  by  subtracting  the  metabol- 
ism during  sexual  rest  from  that  observed  just  before  parturi- 
tion.    By  so  doing  the  following  figures  were  obtained: 

First  pregnancy.  .551.3  —  505.3  =    46     calories  daily  for  one  puppy  of  280 

grams. 
Second  pregnancy.  .764.9  —  505.3  =  259.6  calories  daily  for  five  puppies  of 

1560  grams. 

This  extra  metabolism  was  proportional  to  the  weight  of 
the  puppies  at  birth.  In  the  case  of  the  first  pregnancy  the 
extra  metabolism  was  164  and  in  the  second  165  calories  per 
kilogram  of  puppy  dog  delivered  three  days  later. 

It  is  interesting  to  note  that  the  mother  and  her  five  newly^ 
bom  puppies  together  produced  twice  as  much  heat  as  did  the 
non-pregnant  mother  alone.  The  experiments  were  all  made 
at  a  temperature  of  between  27°  and  28°.  It  is  evident  that  the 
puppies  suckled  by  the  mother  and  exposed  to  the  outside  tem- 
perature had  a  larger  metabolism  than  they  had  had  in  utero. 
For  the  proper  maintenance  of  the  five  offspring  the  mother  with 
a  normal  metabolism  of  505  calories  would  have  to  produce 
mUk  to  provide  for  a  metabolism  of  about  550  calories  in  the 
puppies,  and  still  more  to  furnish  material  for  their  rapid 
growth. 


232 


SCIENCE    OF   NUTRITION. 


Ostertag  and  Zuntz^  report  that  a  sow  may  yield  a  milk 
rich  in  fat  (12.9  per  cent.)  and  in  such  quantity  that  the  energy 
content  may  amount  to  from  two-  to  five-fold  that  required  for 
the  mother  sow's  metabolism. 

An  extraordinary  phenomenon  which  has  been  observed  in 
dogs  and  rabbits  is  that  during  the  early  weeks  of  pregnancy 
there  is  a  loss  of  nitrogen  from  the  mother's  body  even  when 
the  food  ingested  would  be  entirely  sufficient  to  maintain  nitro- 
gen equilibrium  under  usual  circumstances.^  Jageroos  quotes 
Ver  Ecke's  description  of  this  as  "the  sacrifice  of  the  individ- 
ual for  the  good  of  the  species."  It  seems  certain  that  the 
development  of  the  fetus  is  accompanied  by  the  destruction  of 
the  maternal  protoplasm,  perhaps,  as  Murlin  has  suggested, 
in  order  to  afford  hereditary  building  stones  for  the  laying  down 
of  the  youthful  protoplasm  in  accordance  with  the  type  charac- 
teristic of  the  species. 

One  of  Murlin's  experiments  (heretofore  unpublished) 
covering  the  period  of  gestation  in  a  dog  is  given  below: 


WEEKLY   NITROGEN    BALANCE    IN   A    PREGNANT    DOG. 


Week. 


Calories  in 

Food  per 

Day. 


N  IN 

Diet. 


N  TO 

Body 


I.... 
II... 
III.. 
IV.. 
V... 
VI.. 
VII. 
VIII 
IXt 


900 

976* 

976 

976 

976 

976 

976 

976 

976  ** 


54-287 
56.063 
56.063 
56.063 
56.063 
56.063 
56.063 
56.063 
32.036 


63.116 
60.893 
62.031 
64.508 
62.594 
60.064 
54.262 
47.042 
25.867 


—8.83 
—4-83 
—5-97 
-8.44 
—6.53 
■ — 4.00 
+  1.80 
-f  9.02 
+  6.25 


*  69.7  calories  per  kilogram. 
**  61.0  calories  per  kilogram, 
t  Four  days  only. 

^Ostertag   and    Zuntz:  "Landwirtsch.      Jahrbiicher,"   1908,    Ed.    xxxvii, 
p.  226. 

^Hagemann:  "Inaugural  Dissertation"  Erlangen,  1891;  Jageroos:  "Archiv 
fiir  Gynakologie,"  1902,  Bd.  Iviii,  p.  517. 


FOOD   REQUIREMENT   DURING    GROWTH.  233 

This  shows  the  large  loss  of  maternal  protein  commencing 
immediately  after  conception  and  continuing  for  six  weeks. 
Only  during  the  last  two  weeks  is  there  a  marked  conservation 
of  protein  as  manifested  in  the  pronounced  nitrogen  retention. 

Some  very  instructive  experiments  have  been  performed  to 
ascertain  the  course  of  the  protein  metabolism  before  and  after 
pregnancy  in  women. 

Zacharjewski^  investigated  the  nitrogen  metabolism  of  nine 
pregnant  women.  In  three  primiparae  nourished  on  diets  con- 
taining an  average  of  16.5  grams  of  nitrogen,  there  was  an 
average  daily  retention  of  1.4  grams  in  the  mother's  organism 
for  thirteen  days  before  parturition.  In  six  multiparas  the  diet 
contained  20.66  grams  of  nitrogen  and  there  was  a  daily  reten- 
tion of  5.122  grams  of  nitrogen  during  the  last  eighteen  days  of 
pregnancy.  The  figures  correspond  to  a  considerable  con- 
struction of  protein  tissue  within  the  organism.  After  child- 
birth there  was  always  a  loss  of  tissue  nitrogen  by  the  mother. 
In  one  case  nitrogen  equilibrium  was  established  on  the  fifth 
day,  and  in  another  on  the  fourth.  In  six  cases  the  loss  of  body 
nitrogen  continued  over  a  longer  time.  Zacharjewski  says 
that  the  process  of  involution  of  the  uterus  is  greatest  during 
the  first  five  to  seven  days  after  delivery,  and  the  high  nitrogen 
output  from  the  mother  is  the  result  of  this.  After  the  elimi- 
nation which  is  due  to  these  regressive  changes,  there  is  a 
retention  of  nitrogen.  This  is  probably  attributable  to  the 
building  up  of  the  mammary  glands,  for  Siemens^  shows  that 
nitrogen  equilibrium,  once  established,  was  constantly  main- 
tained in  a  woman  who  did  not  nurse  her  child. 

The  complete  record  of  the  nitrogen  elimination  of  a  nursing 
mother,  one  of  Slemons's  cases,  is  here  reproduced.  It  is  espe- 
cially instructive  on  account  of  the  constancy  of  the  quantity  of 
nitrogen  in  the  diet.  The  woman  was  a  ncgress  who  gave 
birth  to  a  healthy,  vigorous  chUd. 

•  Zacharjewski:   " Zcitschrift  fur  Biologic,"  1894,  Bd.  xxx,  p.  405. 

*  Siemens:    "Johns  Hopkins  Hospital  Reports,"  1905,  vol.  xii,  p.  121. 


234 


SCIENCE   OF   NUTRITION. 


PROTEIN  METABOLISM  BEFORE  AND  AFTER  CHILDBIRTH. 
Weights  are  in  Grams. 


Days  Before  and 
After  Delivery. 


9 

8 

7 

6 

5 

4 

3 

2 

I 

Delivery. 
I 

2 

3 

4 

S 

6 

7 

8 

19 

20 

21 

22 

23 

24 

25 


N  IN 

N  IN 

NiN 

N  in 

Food. 

Urine. 

Feces. 

Milk. 

20.5 

11.9] 

19.2 

16.6 

18. 

10.9 

16.9 

17.1 

"■3 

13-7 

19.2 

13-3 

19.2 

12. 1 

0-53 

19.2 

14.1 

18.0 

12.3 

14.9 

12.3 

8.0 

II-5 

4.2 

8.4  J 

7-1 

^3-3 

13-7 

13.2 

0.15 

19. 

15.8 

1.04 

19. 

18.8 

1.99 

20. 

15.6 

2.02 

20. 

21.8 

1. 14 

2. IS 

19. 

18.1 

2.02 

II. 

16.8  J 

2.02 

19.8 

12. 1  ' 

1. 18 

18.8 

^5-3 

1.29 

19.9 

13-3 

1-57 

17-3 

9-7 

1.6 

1.58 

18.3 

13-9 

1.85 

18.75 

11.4 

2.03 

19. 

iS-6. 

1.58^ 

Nin 
Lochia. 


N 
Balance. 


+  8.12 
+  2.07 

+  6.57 
—0.77 

—2-95 
+  5-39 
+  6.57 
+  4-54 
+  5.12 
+  2.06 
— 4.00 

—2.79 
— 0-57 
—4-13 
+  0.15 

-6.5 

—3-14 

—9.2 

+  4-89 
+  0.57 
+  3-39 
+4-39 
+0.68 
+  3.72 
-^.16 


During  the  last  days  of  pregnancy  there  was  an  average 
daily  storage  of  2.98  grams  of  nitrogen,  and  for  eight  days  of  the 
puerperium  an  average  loss  of  4.5  grams.  Later,  between 
the  nineteenth  and  twenty-fifth  days  after  birth  there  was  an 
average  daily  storage  of  2.52  grams  of  nitrogen.  This  may 
have  been  for  the  purpose  of  increasing  the  size  of  the  breasts. 
It  must  be  remembered  that  even  during  the  period  of  involu- 
tion an  increase  in  the  mammary  glands  may  have  been  taking 
place  at  the  expense  of  protein  derived  from  the  uterus.  So 
the  debit  balance  of  nitrogen  during  this  period  may  not  repre- 
sent all  the  protein  change  taking  place. 


FOOD   REQUIREMENT  DURING   GROWTH.  235 

The  mother  had  plenty  of  milk  and  the  baby  gained  an  aver- 
age of  thirty  grams  a  day  during  the  first  forty  days  of  his  life. 

Slemons  remarks  that  the  low  protein  metabolism  as  indi- 
cated by  the  urinarj^  nitrogen  of  the  period  of  settled  lactation 
is  a  proof  that  there  can  be  no  important  production  of  milk 
fat  from  protein. 

In  the  above  experiment  it  will  be  noticed  that  the  nitrogen 
of  the  milk  is  small  in  quantity  as  compared  with  the  urinary 
nitrogen.  On  a  strictly  vegetarian  diet  the  relation  would 
change.  Thus  Voit^  found  48.8  grams  of  nitrogen  in  the  milk 
of  a  cow  and  93.7  grams  of  nitrogen  in  her  urine  for  the  same 
period. 

The  influence  of  nutrition  on  the  production  of  milk  has 
been  the  object  of  countless  investigations,  but  unfortunately 
most  of  these  experiments  have  been  conducted  for  commercial 
purposes  on  cows  and  goats.  These  animals,  with  their  funda- 
mental ration  consisting  of  hay,  do  not  allow  of  the  ingestion 
of  simple  foods.  On  the  other  hand,  the  milk  supply  of  even  a 
large  bitch  is  very  limited  in  quantity  and  is  with  difficulty 
obtained.  The  writer  is  not  aware  of  any  systematic  obser- 
vations on  the  composition  of  human  milk  as  influenced  by 
food,  although  such  researches  would  seem  of  great  impor- 
tance. 

Perhaps  the  most  valuable  research  which  can  to-day  be 
used  is  an  old  one  of  Voit^  upon  a  bitch  weighing  34  kilograms. 
It  confirmed  the  previous  work  of  Kemmerich  and  of  Ssubotin. 
The  animal  was  given  meat  alone,  meat  and  starch,  meat  and 
fat,  starch  alone,  fat  alone,  and  was  also  starved.  The  in- 
fluence upon  the  milk  secretion  was  found  to  be  comparatively 
small.  The  research  is  a  model  of  completeness,  the  plan  of 
which  could  well  be  copied  in  an  experiment  on  a  human 
being. 

'Voit:    "Zeitschrift  fiir  Biologic,"  1869,  Bd.  v,  p.  122. 
^  Voit:   Ibid.,  p.  137. 


236  SCIENCE    OF   NUTRITION. 

A  part  of  the  results  are  given  below: 

INFLUENCE  OF  DIET  ON  THE  COMPOSITION  OF  THE  MILK  OF 
A  DOG  WEIGHING  34  KILOGRAMS. 


Food. 

Milk. 

P 

0 

i 

Other  Food  in 
Grams. 

S 

.9 

d 

i 

<; 

a 

_d 

fa 

1 

.a 

3 

0 

u 

rt  g 

fa 

.as 

6 

7 

8 

9 

JO 

II 

12 

13 

14 

16 

17 

1000 
1000 
1000 

Mixed 
diet 
500 
500 

Starv. 

Starv. 

2000 
2000 

300  starch 
200  fat 
200  fat 

400  starch 
300  fat 

500  starch 

34. 

34- 
34. 

17- 
17- 

68. 
68. 

115 
144 
13s 

ISI 

138 
168 
149 
118 
137 
158 
161 

I.I 
1.4 
I.I 

1.4 
1.2 
1.6 

i.S 

I.O 

I.I 
1.6 
1-7 

8.8 
10.8 
II-3 

13-9 
"•3 
16.S 
13-8 
12.2 
10. 1 
16.1 
14.7 

3-1 
3-8 
2.9 

3-4 
3.8 
4.2 
3.9 

3-0 
4-3 
4.4 
4-7 

5-97 
6.86 
6.22 

6.37 

5.83 
6.06 
6.36 
S.62 
5-41 
6.68 
6.78 

7.70 
7.50 
8.39 

9.22 
8.19 
9.83 
9.24 
10.32 

7-39 
10.17 
9.11 

2.71 

2.67 

2. IS 

2.24 
2.78 
2.52 
2.65 
2.58 
3-II 
2.82 
2.91 

The  largest  quantity  of  milk  as  well  as  the  richest  in  pro- 
tein was  obtained  when  meat  or  meat  and  fat  were  ingested. 
Curiously  enough  a  diet  of  500  grams  of  meat  and  300  grams 
of  fat  gave  milk  of  the  same  amount  and  quality  as  did  2000 
grams  of  meat.  It  is  usually  said  that  a  large  protein  diet 
stimulates  the  milk  secretion;  but  this  may  also  be  due  indirectly 
to  the  development  of  the  gland  cells. 

The  milk  sugar  content  was  scarcely  affected  by  the  diet, 
although  a  slight  percentage  increase  was  observed  after  starch 
ingestion. 

The  fat  content  was  increased  in  starvation  to  its  highest 
percentage.  It  was  not  very  greatly  affected  by  adding  fat  to 
a  meat  diet  and  it  was  greatly  reduced  by  giving  carbohydrates. 

The  action  of  fasting  on  the  fat  content  of  milk  is  better 
shown  in  the  herbivorous  goat.  The  writer^  gave  a  milch  goat 
a  constant  diet  of  hay,  cornmeal,  and  bran,  starved  the  animal 
for  two  days,  and  then  continued  the  former  diet.     The  fat 

^  Lusk:   "Zeitschrift  fiir  Biologic,"  1901,  Bd.  xlii,  p.  42. 


FOOD   REQUIREMENT  DURING  GROWTH.  237 

content  of    the  milk  was  determined.     The  results  were  as 
follows : 

Milk  in  c.c.  Fat  in  G.      Fat  in  per  Cent. 

460 26.50  5.76 

470 25.90  5.52 

^^o o    -  '       >  Starvation. 

198 18.35  9-27  J 

232 1S.75  8.08 

298 16.30  5.47 

348 19-40  5-6i 

362 22.30  6.16 

490 27.70  5.66 

In  fasting,  therefore,  the  fat  content  in  the  milk  of  the  her- 
bivorous goat  approaches  that  contained  in  the  carnivorous 
dog.  With  a  return  to  the  normal  diet  the  fat  content  in  goat's 
milk  is  reduced  to  its  former  level. 

Morgen,  Beger  and  Fingerling^  find  that  a  diet  rich  in  carbo- 
hydrate and  poor  in  fat  produces  in  sheep  and  goats  a  poor 
milk  containing  little  fat,  although  the  general  condition  of  the 
animals  remains  perfect.  Addition  of  protein  increases  the 
quantity  of  the  milk  without  changing  the  low  fat  percentage. 
Replacement  of  some  of  the  carbohydrate  with  isodynamic 
quantities  of  fat,  up  to  0.5  to  i.o  gram  per  kilogram  of  animal, 
largely  increases  the  fat  content  of  the  milk  and  thereby  its 
nutritive  value. 

Contrary  to  this  is  Jordan's^  statement  that  the  amount  of 
fat  in  the  fodder  is  without  influence  upon  the  fat  content  of  a 
cow's  milk.  Here  the  breed  of  the  cow  and  not  the  diet  is  the 
determining  factor.  The  German  agricultural  stations  have 
recently  reached  the  same  conclusion.  Morgen^  states  that  the 
principal  cause  of  the  difference  in  the  results  of  the  experi- 
ments on  cows  and  on  sheep  and  goats  lies  in  the  fact  that  the 
smaller  animals  produce  more  milk  for  their  weight  than  do 

'Morgen,  Beger  and  Fingerling:  "Landw.  Vcrsuchsstationcn,"  1904,  Bd. 
Ixi,  p.  r. 

*  Jordan  and  Jchter:  "New  York  Agricultural  Experiment  Station,"  1897, 
Bulletin  132;   1901,  Bulletin  197. 

•Morgen,  Beger,  Fingerling  and  Wcsthauser:  " LandwirLschaft.  Versuchs- 
stationen,"  1908,  Bd.  Ixix,  p.  295. 


238  SCIENCE   OF   NUTRITION. 

COWS,  and,  therefore,  the  milk  production  is  much  more  depen- 
dent on  the  food  supply. 

It  has  long  been  known  that  ingested  fat  may  appear  in  the 
milk  of  an  animal.  Quite  recently  Gogitidse^  has  shown  that 
after  giving  linseed  oil  to  sheep  their  milk  fat  may  contain  33 
per  cent,  of  linseed  fat.  He  also  finds^  that  the  fat  of  linseed  oil 
passes  readily  into  human  milk,  and  that  the  fat  of  hempseed, 
while  influencing  the  composition  of  the  milk,  greatly  depresses 
lactation  during  the  period  of  its  ingestion. 

How  may  these  various  effects  of  diet  be  explained?  The 
subject  requires  a  knowledge  of  the  processes  going  on  in  the 
mammary  gland  and  these  are  not  certainly  known.  It  has  been 
generally.believed  that  the  cells  of  the  mammary  glands  under- 
go a  fatty  metamorphosis  and,  themselves  breaking  up,  pass  into 
the  milk  (Voit,  Heidenhain).  The  milk  under  these  circum- 
stances might  be  regarded  as  the  substance  of  an  organ,  made 
fluid. 

Schafer,^  however,  believes  the  process  to  be  one  of  secretion 
similar  to  that  in  the  salivary  glands,  where  the  cells  prepare 
the  special  constituents  and  pass  them  on  to  the  lumen.  Thus 
casein,  like  ptyalin,  may  be  specially  elaborated  within  gland 
cells. 

If  this  be  the  true  explanation,  the  influence  of  food,  in  the 
writer's  opinion,  may  be  readily  explained.  An  increased  pro- 
tein ingestion  furnishes  the  digestive  products  of  this  sub- 
stance in  liberal  quantities  and  may  increase  the  activity  of  the 
gland. 

The  milk  sugar  content  of  the  milk  remains  remarkably 
constant.  Cremer,*  for  example,  has  shown  that  the  percentage 
of  milk  sugar  in  the  milk  is  unchanged  in  the  cow  after  dimin- 
ishing the  sugar  content  of  the  animal  by  inducing  phlorhizin 
diabetes. 

*  Gogitidse:   "Zeitschrift  fur  Biologie,"  1904,  Bd.  xlv,  p.  365. 
^  Gogitidse:  Ibid.,  1905,  Bd.  xlvi,  p.  403. 

'  Schafer:   "Text-book  of  Physiology,"  1898,  vol.  i,  p.  667. 

*  Cremer:   " Zeitschrif t  fiir  Biologie,"  1898,  Bd.  xxxvii,  p.  78. 


FOOD   REQUIREMENT   DURING   GROWTH.  239 

To  explain  the  fat  content  of  the  milk,  the  writer  offers  the 
following  theory:  When  for  any  reason  sufficient  sugar  is 
not  oxidized  in  the  body  cells,  these  sugar-hungry  cells  attract 
fat.  It  has  already  been  seen  that  the  glycogen  and  fat  content  of 
the  liver  are  antagonistic.  Before  lactation  sets  in,  the  cells 
of  the  mammary  glands  oxidize  sugar  and  there  is  no  great 
attraction  for  fat.  It  is  believed  that  milk  sugar  cannot  be 
formed  in  any  great  quantity  before  parturition,  because  it 
occurs  in  the  urine  only  post  partiim}  That  milk  sugar  is 
not  formed  outside  of  the  mammary  glands  was  demon- 
strated by  Moore  and  Parker,'  who  completely  removed  these 
glands  from  a  goat  during  the  period  of  gestation,  and  later 
at  the  time  of  parturition  found  no  sugar  in  the  urine.  Had 
milk  sugar,  which  cannot  be  oxidized  by  the  organism,  been 
formed  outside  the  glands  it  would  have  accumulated  in  the 
blood  and  have  been  eliminated  in  the  urine.  When  in  the 
process  of  lactation  the  dextrose  furnished  by  the  blood  is 
converted  into  milk  sugar  (which  cannot  be  burned  within 
the  organism),  the  mammary  cell  becomes  a  sugar-hungry 
ceU  which  at  once  attracts  fat  from  the  blood.  This  theory 
of  the  writer  explains  the  production  of  milk  fat  by  the  pro- 
cess of  infiltration.  The  variation  of  the  percentage  of  fat  in 
the  milk  may  be  explained  by  the  quantity  of  fat  in  the  blood. 
During  starvation  the  blood  becomes  rich  in  fat  on  account  of 
the  transportation  of  tissue  fat  to  the  cells.  Administration  of 
sugar  at  once  reduces  the  supply  of  fat  in  the  blood.  But  if  fat 
be  ingested  with  carbohydrates  the  blood  becomes  rich  with  this 
fat  and  affords  material  for  a  rich  milk. 

Administration  of  good  cream  with  a  substantial  mixed  diet 
is  highly  to  be  recommended  for  nursing  mothers.  The  daily 
production  of  a  liter  of  milk,  which  has  a  value  of  640  calories, 
indicates  the  necessity  of  no  small  addition  to  the  daily  ration, 

*  Lemairc:  "Zeitschrift  f ilr  physiologische  Chemie,"  1896,  Bd.  xxi,  p.  442. 
'Moore  and  Parker:  "American   Journal  of  Physiology,"    1900,  Bd.  iv, 
p.  239. 


240  SCIENCE   OF   NUTRITION. 

if  the  woman  is  to  bear  satisfactorily  the  strain  of  lactation. 
Probably  this  extra  nourishment  is  best  given  in  the  form  of  fat. 

Should  the  fat  of  the  milk  disagree  with  the  infant,  the 
trouble  may  be  due  to  the  kind  of  fat  ingested  by  the  mother. 
If,  however,  the  indigestion  be  due  to  a  large  percentage  of  fat, 
a  carbohydrate  diet  may  be  used  to  reduce  the  percentage  in  the 
milk. 

A  very  important  fact  regarding  the  nutrition  of  the  young 
is  that  the  milk  of  one  race  is  specifically  adapted  to  the  growth 
of  the  offspring  of  that  particular  race.  Bunge^  found  that  dog's 
milk  had  an  ash  of  exactly  the  same  composition  as  the  ash  of 
the  new-born  puppy.  The  ash  of  the  milk  was  therefore  per- 
fectly adapted  for  the  construction  of  new  puppy  tissue.  It 
was,  however,  very  different  in  composition  from  human,  or 
cow's,  or  other  milk.  Only  in  the  case  of  iron  is  the  quantity 
lower  than  corresponds  to  the  composition  of  the  offspring, 
but  this  factor  is  offset  by  the  fact  that  the  animal  when  new- 
bom  is  richer  in  iron  than  it  is  at  any  other  period  of  life.  Not 
only  this,  but  the  caseins  of  different  milks  are  different  in 
chemical  behavior.  And  besides  this,  the  rennin  of  the  stom- 
ach is  said  to  be  specifically  adapted  for  the  coagulation  of  the 
casein  produced  by  the  female  of  the  same  race.^ 

Furthermore,  the  percentage  quantity  of  the  constituents  in 
the  milk  is  dependent  upon  the  rapidity  of  the  growth  of  the 
organism.  Bunge^  has  shown  this  in  the  following  comparative 
table : 

Time  in  Days  for 
THE  New-born 
Animal  to  ioo  Parts  of  Milk  Contain 

Double  its  Weight.     Protein.        Ash.        Calcium  Oxid. 

Man i8o  1.6  0.2  0.0328 

Horse — 60  2.0  0.4  0.124 

Calf 47  3.5  0.7  0.160 

Kid 19  4.3  0.8  0.210 

Pig 18  5.6  ..                

Lamb 10  6.5  0.9  0.272 

I^og 8  7.1  1.3  0.4S3 

Cat 7  9.5  ..                

^  Bunge:   "Zeitschrift  fiir  Biologie,"  1874,  Bd.  x,  p.  326. 

^Kiesel:   "Pfliiger's  Archiv,"  1905,  Bd.  cviii,  p.  343. 

^  Bunge:   "Lehrbuch  der  physiologischen  Chemie,"  1898,  p.  118. 


FOOD   REQUIREMENT   DURING    GROWTH.  24I 

Camerer^  finds  that  human  milk,  drawn  three  to  twelve 
days  after  parturition,  contains  0.2  milligram  of  iron  (Fe203) 
per  100  c.  c,  while  the  later  milk  contains  o.i  milligram.  The 
quantity  is  decreased  if  the  environment  or  the  condition  of  the 
mother  be  poor.^  Using  the  customary  methods  of  infant 
feeding  with  cow's  milk,  the  infant  obtains  too  little  iron. 

Blauberg^  reports  the  following  percentage  absorption  of 
the  ash  of  cow's  and  human  milk: 


Per  Cent.  Milk 

Kind  of  Milk.                                                              Subject.  Ash  Absorbed. 

Cow's Infant.  60.70 

Diluted  cow's "  53-72 

Human "  79-42 

Human "  81.82 

Cow's Adult.  53.20 


The  quantity  of  calcium  in  cow's  milk  is  in  excess  of  the 
needs  of  the  human  infant. 

The  absorption  of  the  energy-containing  constituents  of  the 
milk  is  remarkably  constant.  This  is  illustrated  in  the  follow- 
ing table  made  from  Rubner's  experiments,^  which  shows  the 
physiological  utilization  of  the  total  calories  of  milk: 

Per  Cent,  of  Calories 
Absorbed. 

Human  milk 91.6  to  94.0 

Diluted  cow's  milk 90-7 

Diluted  cow's  milk  +  milk  sugar 92.2 

Same  given  to  stunted  infant 87.1 

Cow's  milk  given  to  an  adult 89.8 

As  regards  the  relative  composition  of  average  cow's  and 
human  milk  five  and  a  half  months  after  parturition,  tlic  fol- 
lowing comparison  may  be  made: 

»  Camercr:   "Zeitschrift  fiir  Biologic,"  1905,  Bd.  .xlvi,  p.  371. 

*  JoUes  and  Friedjung:  "Arch,  fur  experimentellc  Path,  und  I'harm.," 
1901,  Bd.  xlvi,  p.  247. 

•Blaubcrg:   "Zeitschrift  fur  Biologic,"  1900,  Bd.  xl,  p.  44. 

*  Rubncr:  Ibid.,  1899,  Bd.  xxxviii,  p.  380.  For  further  statistics  of  ab.sorii- 
tion  consult  Tangl:   "Pfluger's  Archiv,"  1904,  Bd.  civ,  p.  853. 

16 


242  SCIENCE    OF   NUTRITION. 

PERCENTAGE    COMPOSITION    OF    COW'S    AND    HUMAN   MILK. 

Cow's.  Human. 

I.l  II.2  1.3  II.* 

Protein 3.41  3-2  i-o  i-S^ 

Fat 3.65  3.9  3.0  3.28 

Milk  sugar 4-8i  5-i  6.4  6.50 

Or,  expressed  in  the  relative  calorific  value  of  the  different 
constituents  this  comparison  may  be  given  :^ 

PERCENTAGE    DISTRIBUTION    OF    CALORIES    IN    COW'S    AND 
HUMAN  MILK. 

Cow's.  Human. 

I.  I. 

Protein 21.3  7.4 

Fat 49-8  43-9 

Milk  sugar 28.9  48.7 

Here,  then,  there  are  tremendous  differences  of  composition 
which  fact  forces  the  conclusion  that  cow's  milk  is  not  to  be  sub- 
stituted for  human  milk  in  rearing  a  child. 

Patein  and  DavaP  find  that  human  milk  after  the  first 
month  of  lactation  contains  but  0.8  to  i  per  cent,  of  casein. 

Another  distinction  between  cow's  and  human  milk  is  that 
the  former  contains  but  little  extractive  nitrogen  while  the  latter 
may  contain  18  to  20  per  cent.''  in  that  form.  These  nitrogen- 
ous extractives  contain  a  considerable  amount  of  carbon.  This 
is  probably  one  of  the  causes  of  the  increase  of  the  -~  ratio 
(p.  36)  to  over  one  in  the  urine  of  breast-fed  infants. 

The  large  protein  content  of  cow's  milk  may  be  bad  for  the 
child.  In  the  first  place  it  clots  in  a  heavy  mass  in  the  baby's 
stomach;  and  in  the  second  place,  even  though  it  be  digested,  it 

^  Rubner:  Von  Leyden's  "Handbuch,"  1903,  Bd.  i,  p.  95. 

^  Van  Slyke,  "Modern  Methods  of  Testing  Milk  and  Milk  Products,"  1907. 
Average  of  5552  American  analyses. 

^Rubner  and  Heubner:  "Zeitschrift  fiir  ex.  Pathologie  und  Therapie," 
1905,  Bd.  i,  p.  I. 

*S6ldner:  "Zeitschrift  fiir  Biologie,"  1896,  Bd.  xxxiii,  p.  66.  Average  of 
the  milk  of  five  v^omen. 

*  Rubner:   "  Energiegesetze,"  1902,  p.  418. 

^  Patein  and  Daval:  "  Journal  de  Pharm.  et  de  Chimie,"  1905,  T.  xxi,  p.  193. 

'  Rubner  and  Heubner:    Loc.  cit. 


POOD   REQUIREMENT   DURING    GROWTH. 


243 


is  relatively  much  above  the  requirement  of  the  organism,  and 
its  specific  d}Tiamic  action  increases  the  amount  of  heat  pro- 
duced. 

If  cow's  milk  be  diluted  with  two  or  more  parts  of  water,  its 
protein  content  may  approach  that  of  human  milk  and  its  pre- 
cipitation by  rennin  in  the  stomach  is  in  the  form  of  flakes. 
This  precipitation  of  cow's  casein  takes  place  in  even  finer 
flakes  when  the  milk  is  mixed  with  barley  water,  as  was  shown 
by  Chapin. 

Chapin's  observations,  in  which  the  writer  assisted,  have 
been  confirmed  by  White,^  who  says  that  this  action  is  due  to 
the  presence  of  three-fourths  to  one  per  cent,  of  dissolved  starch. 

The  dilution  of  cow's  milk,  however,  reduces  the  quantity 
of  fat  and  carbohydrates,  and  these  must  therefore  be  added  to 
the  milk  in  order  to  make  a  proper  diet  for  a  child. 

To  obtain  a  sufficient  fat  content,  "top  milk,"  rich  in  fat, 
may  be  taken  from  milk  which  has  been  standing,  and  may  be 
mixed  with  water.     Milk  sugar  may  then  be  added. 

Such  a  milk,  called  "modified  milk,"  was  first  introduced 
by  Rotch  of  Boston.  Infants  are  brought  up  on  it  with  greater 
success  than  was  the  case  when  undiluted  cow's  milk  was  given. 

Human  milk  has  a  varying  calorific  value  dependent  largely 
on  the  amount  of  fat  present.  Thus  Schlossmann^  finds  that  the 
calorific  value  per  liter  of  nineteen  samples  of  milk  from  nine- 
teen women  averages  719  calories,  with  a  maximum  of  876 
and  a  minimum  of  567.  The  milks  having  the  largest  fuel 
value  contained  5.2  to  5.1  per  cent,  of  fat,  while  that  having  the 
lowest  contained  only  1.8  per  cent. 

The  amount  of  the  child's  metabolism  is  dependent  on 
his  size.  Rubner  states  that  a  baby  weighing  4  kilograms 
produces  422  calorics,  an  adult  weighing  40  kilograms,  2106 
calories.     But  the  metabolism  per  unit  of  area  is  the  same. 

'White:  "Journal  of  the  Boston  Society  of  Medical  Sciences,"  1900,  vol. 
V,  p.  130. 

*  Schlossmann:  "Zeitschrift  fiir  physiologische  Chemie,"  1903,  Bd.  xxxvii, 
p.  340. 


244  SCIENCE    OF   NUTRITION. 

Rubner  and  Heubner^  summarize  their  results  on  the  metab- 
olism of  differently  conditioned  children  as  follows: 

Calories  per  Sq. 
Weight  in  Kg.        Meter  of  Surface. 

Infant  of  stunted  growth 3  1090 

"       at  the  breast 5  1006 

"       on  cow's  milk 8  1143 

"       at  the  breast 10  1219 

The  metabolism  in  all  these  cases  was  essentially  the  same 
per  unit  of  area. 

In  the  last  case  the  very  noticeable  amount  of  muscle  move- 
ment and  crying  while  the  child  was  in  the  respiration  appa- 
ratus increased  the  metabolism.  Further  details  regarding  this 
case  give  a  very  complete  picture  of  the  metabolism  of  an  infant. 
The  child  weighed  4.06  kilograms  at  birth,  and  about  lo  kilo- 
grams at  the  time  of  the  experiment  when  live  and  a  half  months 
old.     He  was  given  his  mother's  milk. 

The  first  day  of  the  experiment  the  child  was  very  uncom- 
fortable on  account  of  his  new  environment.  The  last  day  he 
was  given  only  a  small  quantity  of  tea,  and  was  therefore  in 
a  state  of  practical  starvation.  The  carbon  dioxid  excretion  on 
these  days  was  as  follows: 

Grams  of  CO2 
Day.  in  24  Hours. 

First 278.8 

Second 219.9 

Third 228.1 

Fourth 231. 1 

Fifth 218.2 

The  diet  on  the  second,  third,  and  fourth  days  consisted  of 
1258  grams  of  human  milk  per  day  containing: 

Total  nitrogen 1.99  grams. 


Fat 


37-73 


Milk  sugar 80.5 

Of  the  total  nitrogen  only  1.63  grams  were  contained  in  true 
protein,  the  rest  being  in  nitrogenous  extractives.     The  per- 

^  Rubner  and  Heubner:    "Zeitschrift  fiir  ex.   Pathologic  und  Therapie," 
1905,  Bd.  i,  p.  I. 


FOOD    REQUIREMENT   DURING    GROWTH, 


245 


centage  composition  of  this  milk  is  given  on  page  242.     Its 
actual  nutritive  value  was  634.5  calories. 

The  balance  sheet  of  the  respiration  experiment  showed  the 
following  daily  result : 

METABOLISM  OF  AN  INFANT. 


< 

' 

< 
Q 

1 

Q 
0 
0 

g 

g 

g 
15 

0 
z 

< 

<: 
a 

0 
0 

0 
t, 

g 

C  IN  EXCREI 

8 

z 

< 

u 

Grams. 

Grams. 

Grams. 

Grams. 

Grams. 

Grams. 

Grams. 

2,  3.  4- 

Milk 

1.99 

1-13 

1-53 

+  0.46 

63.7 

65.8 

— ^2.1 

5 

None 

1. 18 

1. 18 

—1. 18 

60.8 

—60.8 

The  infant  was  nearly  in  calorific  equilibrium  during  the 
period  of  milk  ingestion.  There  were  634.5  available  calories 
in  the  milk  and  660.5  calories  produced  in  the  metabolism. 

The  quantity  of  the  protein  metabolism  was  extremely 
small,  being  9.6  grams  according  to  the  usual  method  of  com- 
putation. The  milk  contained  protein  to  the  extent  of  7  per 
cent,  of  its  total  calorific  content.  Of  this  only  5  per  cent,  was 
metabolized  and  2  per  cent,  was  added  to  the  body.  The 
metabolism  of  an  infant  may  therefore  be  maintained  on  a  diet 
in  which  5  per  cent,  of  the  energy  is  supplied  by  protein  and 
95  per  cent,  by  fats  and  carbohydrates. 

The  specific  dynamic  action  of  the  milk  was  almost  negli- 
gible, the  metabolism  being  approximately  the  same  during  the 
period  of  feedhig  as  during  that  of  starvation.  Curiously 
enough,  the  protein  metabolism  was  the  same  on  days  of  milk 
ingestion  as  in  starvation.  The  "wear  and  tear"  quota  was 
covered  by  a  "repair"  quota  of  equal  amount.     (See  p.  187.) 

This  child  gained  normally  in  weight  before  and  after  the 
respiration  experiment,  but  during  that  time,  struggling  and 
crying  prevented  fat  addition  to  the  otherwise  wcll-dcvcloi)cd 
normal  infant.^ 

'Hcubncr:   "  Jahrlju(  h  fur  Kindcrhcilkundc,"  1905,  Bil.  Ixi,  Heft  3. 


246  SCIENCE    OF   NUTRITION. 

W.  Camerer,  Jr./  showed  that  a  breast-fed  infant  nine 
months  old  may  ingest  480  calories  in  the  milk,  produce  420 
calories  in  metabolism  and  add  60  calories  to  his  body,  or  15 
per  cent,  of  the  energy  content  of  the  diet.  In  this  case  40  per 
cent,  of  the  protein  intake  was  added  to  the  growing  organism. 

Rubner  and  Heubner^  have  reported  a  respiration  experi- 
ment on  a  child  seven  and  a  half  months  old,  nourished  with 
modified  cow's  milk.  The  intake  was  682.8  calories,  the 
metabolism  593.2,  leaving  89.6  calories  or  12.2  per  cent,  for 
addition  to  the  child's  organism. 

It  is  remarkable  that  a  child's  intuitive  appetite  should 
determine  the  ingestion  of  nutriment  necessary  to  cover  the 
energy  requirement  of  his  organism,  and  a  small  addition  for 
normal  development.  A  reduction  of  15  per  cent,  in  the  intake 
of  food  would  bring  his  prosperous  growth  to  a  standstill. 

Heubner^  says  that  the  average  normal  infant  requires  100 
calories  per  kilogram  of  body  weight  for  normal  nutrition  dur- 
ing the  first  three  months  of  his  life;  90  calories  during  the 
second  three  months,  and  80  and  less  thereafter.  The  energy 
content  of  the  food  should  never  sink  below  70  calories  per 
kilogram,  which  is  about  the  maintenance  minimum. 

The  so-called  "scientific  feeding"  of  infants  is  unworthy  of 
the  name  unless  the  calorific  requirement  is  carefully  consid- 
ered. From  lack  of  this  knowledge  babies  are  frequently  sys- 
tematically starved. 

Oppenheimer*  first  called  attention  to  the  fact  that  the  growth 
in  grams  of  normal  breast-fed  children  of  the  same  age,  maybe 
nearly  proportional  to  the  quantity  of  milk  ingested.  Here  the 
milk  presumably  had  the  same  calorific  value  throughout  the  ex- 
periment although  this  could  not  be  determined.  The  quantity 
of  milk  taken  at  each  meal  was  found  by  weighing  the  infant 

^W.  Camerer,  Jr.:  "Zeitschrift  fiir  Biologic,"  1902,  Bd.  xliii,  p.  i. 
^Rubner  and    Heubner:     "Zeitschrift  fiir    Biologic,"  1899,    Bd.    xxxviii, 
P-  345- 

^Heubner:   "Berliner  klinische  Woclicnsclirift,"  1901,  p.  449. 
^  Oppenheimer:   "Zeitschrift  fiir  Biologie,"  1901,  Bd.  xlii,  p.  147. 


FOOD  REQUIREMENT  DURING   GROWTH. 


247 


before  and  after  nursing, 
duced : 


Oppenheimer's  table  is  here  repro- 


MONTH, 
I.. 
II.. 
Ill 


GROWTH  IN  GR.\]MS  FOR  i  KG.  MILK. 

Oppenheimer's 
Subject. 

95 -o 
201. 1 

138.5 


Peer's 
Subject. 

33-8 

191-2 

120.3 

IV 102.6 

Y.'.'..... 57  7 


103.3 
120.8 


The  proportion  of  growth  to  milk  given  was  practically  the 
same  during  the  second,  third,  and  fourth  months  of  these 
children's  lives. 

That  the  growth  of  suckling  pigs  may  be  proportional  to  the 
calorific  value  of  the  milk  has  been  shown  by  work  accomplished 
by  Dr.  L.  C.  Sanford  and  Dr.  Margaret  B.  Wilson'  in  the 
writer's  laboratory.  Newly  born  pigs  of  two  litters  were  reared 
on  skimmed  cow's  milk  and  on  the  same  milk  fortified  with 
two  and  three  per  cent,  of  glucose  or  of  milk  sugar.  The 
experiments  were  continued  from  fourteen  to  sixteen  days.  The 
results  obtained  in  these  experiments  are  thus  tabulated: 

GROWTH  OF  SUCKLING  PIGS. 


Weight  in  grams  when 
bom 

Weight  in  grams  when 
killed 

Growth  in  grams  .... 
Growth  in  per  cent. . . 

Milk  fed  in  c.c 

AvailaVjle  calories  fed 
Growth  in  grams  per 

liter  of  milk.. 
Growth  in  grams  per 

1000  calories  fed  . 


Wilson. 

Skim. 

Lactose. 

1322 

1295 

2205 
883 
66.8 

2435 
1 140 
88.0 

10925 
4053 

1 1005 
5216 

81 

114 

218 

1 

215 

Dex- 
trose. 


1485 

2471 

986 

64.4 

9707 

4620 


213 


Sanford  and  Lusk. 


Skim. 


1264 

264 

26.4 

6826 

2339 

38 

114 


Lactose. 


1050 

1890 
838 

79.7 
8836 

3736 

95 
222 


Dex- 
trose. 


1152 

2000 
848 

73.' 
9481 

3972 

89 

213 


•Wilson:  "American  Journal  of  Physiology,"  1902,  vol.  viii,  i).  197. 


248  SCIENCE    OF   NUTRITION. 

It  is  seen  that  the  growth  of  the  pigs  in  grams  was  directly 
proportional  to  the  calorific  value  of  the  food  to  the  organism. 
The  one  exception  was  that  of  an  ill-nourished  pig  fed  with 
skimmed  milk.  This  was  an  improperly  nourished  animal 
taking  too  little  food  and  remaining  behind  his  fellows  in  normal 
development.  But  that  five  out  of  six  pigs  of  different  litters, 
of  different  sizes  and  differently  fed,  should  have  gained  in 
weight  respectively  213,  214,  215,  218,  and  222  grams  per  thou- 
sand calories  in  the  food  ingested  seems  more  than  a  coincidence. 

It  may  be  further  calculated  that  to  form  i  kilogram  of 
body  substance  containing  28.7  grams  of  nitrogen  and  866 
calories,  required  the  ingestion  of  4637  calories  in  the  food. 

A  pig  doubles  in  weight  in  eighteen  days  after  birth.  The  pig 
of  Dr.  Wilson,  brought  up  on  skimmed  milk  with  3  per  cent, 
of  milk  sugar  added,  nearly  doubled  in  weight  in  sixteen  days. 

Comparing  the  fuel  value  of  sow's  milk  and  that  of  the 
skimmed  cow's  milk  to  which  milk  sugar  had  been  added, 
the  following  results  are  significant.  Of  100  calories  in  the 
food  there  are : 

Sktm  Milk  +  3  Per 
Sow's  MiLK.i  Cent.  Milk  Sugar. 

Protein 19.5  36.5 

Fats 72.0  2.5 

Carbohydrates 8.5  61.0 

It  is  apparent  from  this  that  normal  growth  of  the  young 
organism  may  be  attained  by  the  replacement  of  fat  by  milk 
sugar  in  isodynamic  quantity.  This  fact  may  become  of  impor- 
tance in  infant  feeding. 

Dr.  Wilson  found,  when  the  pigs  reared  on  these  diets 
were  killed  and  their  composition  compared  with  that  of  three 
pigs  of  the  same  litter  which  were  killed  at  birth,  that  there  was  a 
retention  for  growth  of  i8  to  19  per  cent,  of  the  energy  in  the 
food.  This  retention  of  a  definite  nutrient  factor  is  a  necessary 
corollary  to  the  fact  of  the  growth  being  proportional  to  the 
calorific  intake. 

^  Calculated  from  Ostertag  and  Zuntz :  "  Landwirtsch.  Jahrbiicher," 
1908,  Bd.  xxxvii,  p.  211. 


FOOD    REQUIREMENT   DURING    GROWTH.  249 

In  children  Camerer  found  15  per  cent.,  Rubner  and  Heub- 
ner  12.2  per  cent,  so  retained. 

The  percentage  of  calcium  (CaO)  in  the  dry  solids  of  the 
pigs  reared  on  the  various  skim  milks  was  8.29,  8.02,  and  8.13, 
showing  that  the  absorption  of  calcium  depended  on  the  growth 
of  the  organism,  and  not  on  a  variation  in  the  quantity  ingested. 

There  is  apparently  a  fixed  and  definite  tendency  towards 
uniform  growth.  Schapiro^  found  that  if  young  kittens  were 
chloroformed  twice  daily  their  growth  was  retarded  in  compari- 
son with  normal  control  animals.  However  on  stoppage  of 
the  chloroform  treatment,  the  greater  rapidity  of  growth  during 
an  after  period  fully  compensated  for  the  earlier  delay  in  de- 
velopment. 

Another  instance  which  demonstrates  that  the  young  organ- 
ism may  grow  in  proportion  to  the  energy  ingested  in  the  food, 
is  brought  to  light  by  calculations  based  on  the  work  of  E. 
Rost.^  This  author  gave  meat,  fat  and  bone-ash  to  three  dogs 
of  the  same  litter,  the  experiment  starting  on  the  ninety-eighth 
day  of  their  lives  and  continuing  eighty-eight  days.  The 
writer  has  thus  calculated  the  results : 

Dog  I.  Dog  II.  Dog  III. 

Weight  in  grams  at  start 3,200  2,200  4,150 

Weight  in  grams  at  end 6,280  4,620  8,750 

Growth  in  grams 3,080  2,440  4,600 

Growth  in  per  cent 96  no  no 

Available  calories  ingested 24,420  17,336  34,276 

Gain  in  grams  per  1000  calories 

ingested 122  141  134 

It  is  worthy  of  note  that  these  growing  dogs,  fed  with  meat 
and  fat,  gained  in  weight  nearly  the  same  number  of  grams 
per  1000  calories  ingested  in  the  food.  This  law  of  growth 
seems  reasonably  established.  It  simply  expresses  the  fact 
that  during  the  normal  development  of  the  young  of  the  same 

'  Schapiro:  Proc.  of  the  Physiol.  Society, "  Journal  of  Physiology,"  vol.  xxxiii, 
p.  xxxi. 

^Rost:  "Arbeiten  aus  dem  kaiscrlichen  Gesundhcitsamle,"  1901,  Hd.  xviii, 
p.  206. 


250  SCIENCE    OF   NUTRITION. 

age  and  species,  a  definite  percentage  of  the  food  is  retained 
for  growth  irrespective  of  the  size  of  the  individual. 

Rubner^  in  apparent  ignorance  of  this  work  of  Dr.  Wilson,  has 
arrived  at  essentially  the  same  conclusions,  and  he  finds  that 
the  law  is  true  regarding  all  species  (horse,  calf,  sheep,  pig,  dog, 
cat,  rabbit)  except  man.  He  formulates  the  "law  of  constant 
energy  expenditure"  as  follows:  The  amount  of  energy  (calories) 
which  is  necessary  to  double  the  weight  of  the  newly  born  of  all 
species  (except  man)  is  the  same  per  kilogram  no  matter  whether 
the  animal  grows  quickly  or  slowly.  To  construct  one  kilogram 
of  normal  body  substance  containing  30  grams  of  nitrogen 
and  1722  calories,  4808  calories  are  required  except  in  the  case 
of  man,  where  six  times  that  amount  is  needed. 

Rubner  finds  in  all  species  the  constant  retention  of  approxi- 
mately the  same  percentage  of  the  energy  ingested,  which 
averages  34.3  per  cent.,  except  in  the  case  of  man,  where  the 
energy  retained  for  growth  is  only  5.2  per  cent.  He  states  that 
40  per  cent,  of  the  energy  ingested  may  be  retained  for  the 
growth  of  pigs,  whereas  Dr.  Wilson  found  only  20  per  cent,  so 
retained.  This  is  because  the  pigs  in  the  latter  case  were  given 
skimmed  milk  and  the  added  tissue  substance  was  found  on 
analysis  to  have  a  heat  value  of  only  866  calories  per  kilogram, 
instead  of  1722  as  assumed  by  Rubner. 

It  is  therefore  evident  that  while  it  requires  the  same  energy 
equivalent  to  construct  one  kilogram  of  new  substance  in  young 
animals,  the  percentage  of  energy  retained  for  growth  may 
depend  upon  the  amount  of  fat  in  the  diet. 

Rubner  states  that  if  the  requirement  for  energy  in  the 
various  animals  be  placed  at  100,  then  the  amount  of  energy  in 
the  food  actually  ingested  by  them  averages  202.  This  corre- 
sponds to  Dr.  Wilson's  computation  of  the  energy  ingested  by 
the  growing  pigs,  which  averaged  2100  calories  per  square 
meter  of  surface,  as  compared  with  a  normal  requirement  of 

^  Rubner:  "Das  Problem  der  Lebensdauer  und  seiner  Beziehung  zu  Wachs- 
tum  und  Ernahrung,"  1908. 


FOOD   REQUIREMENT  DURING   GROWTH. 


251 


1089.  Dr.  Wilson  explained  this  high  energy  requirement  as 
being  partly  due  to  growth  and  partly  to  the  extreme  activity 
of  the  little  animals.  A  human  infant  does  not  require  this 
large  excess  of  energy  in  his  food,  probably  because  he  is  kept 
warm  and  sleeps  much  of  the  time. 

Finally  Rubner  has  calculated  that  the  quantity  of  energy 
metabolized  in  a  kilogram  of  living  cells  from  maturity  to  death 
is  the  same  in  different  animals,  except  in  the  case  of  man,  who 
again  occupies  an  exceptional  position. 

This  is  represented  in  the  following  table : 


Body  weight 
IN  Kg. 

Length  of 

Life  in  Years 

AFTER  Maturity. 

Calories  Produced 
Per  I  Kg.  Adult 
Body-Substance. 

Man 

Horse 

Cow 

Dog 

Cat 

Guinea-pig 

60. 
45°- 
45°- 

22. 

3- 
0.6 

60 

30 
26 

9 
8 
6 

775.770 
169,900 
141,090 
163,900 
223,800 
265,500 

Rubner  finds  that  among  the  animals  each  kilogram  of 
adult  body  substance  metabolizes  an  average  of  191,600  calories 
and  then  dies.  Man  alone  has  power  in  his  protoplasm  to  use 
a  much  larger  share  of  energy  in  the  furtherance  of  his  activities. 


TABLE  SHOWING  FLOURENS'  LAW  OF  LONGEVITY. 


Man.. 
Camel 
Horse . 
Cow.. 
Lion . . 
Cat... 
Dog.. 


Time  in  Days 
from  Birth 
TO  Double 

Birth-weight. 


180 

60 
47 

'9i 
9 


Time  in 

Years  Until 

Full 

Growth. 


5 
4 
4 


Deduced 
Average  Lon- 
gevity in 
Years. 


90-100 

40 

25 
15-20 

30 

9-10 

10-12 


Maximum  Re- 
corded Lon- 
gevity IN 
Years. 


152-169 

100 

5° 

60 
20 
24 


252  SCIENCE    OF   NUTRITION. 

Bunge^  has  recently  recalled  the  relationship  between  ra- 
pidity of  growth  and  longevity,  as  originally  suggested  by 
Flourens  in  1856.  This  writer  believed  that  if  the  time  of  reach- 
ing the  end  of  growth  be  multiplied  by  fi,ve,  the  average  term 
of  life  might  be  computed.  This  relationship  may  be  tabu- 
lated as  shown  on  p.  251. 

Bunge  calls  attention  to  the  fact  that  a  horse  more  often 
lives  to  be  forty  than  a  man  to  be  a  hundred.  Either  the  law 
is  false,  or  man  is  a  too  early  victim  of  an  improper  heredity 
or  environment. 

For  metabolism  in  youth,  see  page  170. 

*Bunge:   "Pfliiger's  Archiv,"  1903,  Bd.  xcv,  p.  606. 


CHAPTER  XI. 

METABOLISM  IN  ANEMIA,  AT  HIGH  ALTITUDES,  IN 
MYXEDEMA,  AND  IN  EXOPHTHALMIC  GOITER. 

In  man  one-thirteenth  part  of  the  body  weight  is  carried  as 
blood  to  the  lungs  at  least  every  minute  and  there  exposed  for 
a  period  of  two  seconds  to  the  action  of  the  alveolar  air.  The 
blood  in  the  capillaries  of  the  lungs  may  be  estimated  as  a  film 
o.oi  millimeter  in  thickness,  and  150  square  meters  in  area,  or 
nearly  a  hundred  times  the  area  of  the  surface  of  the  body. 
Zuntz  estimates  the  combined  thickness  of  the  alveolar  wall  and 
capillary  wall  at  0.004  mm.  This  is  the  total  distance  sepa- 
rating the  alveolar  air  from  the  blood.  The  gaseous  exchange 
between  the  air  and  the  blood  is  thus  readily  made  possible. 
Complete  deprivation  of  oxygen  results  in  asphyxiation  and 
death. 

The  question  arises,  Will  there  be  any  effect  upon  metabolism 
if  the  oxygen  supply  for  the  body  be  reduced  ?  Such  a  reduc- 
tion of  oxygen  available  for  the  tissues  might  be  brought  about 
bv  bloodletting,  anemia,  carbon-monoxid  poisoning,  by  life  on 
high  mountains,  or  in  balloons  at  high  altitudes,  or  in  pneu- 
matic cabinets  at  reduced  pressure,  or  by  the  artificial  restric- 
tion of  the  free  influx  of  atmospheric  air  into  the  lungs.  Any 
of  these  methods  if  carried  beyond  a  certain  point  is  known  to 
produce  death. 

It  was  noted  by  Lavoisier  and  confirmed  by  Regnault  and 
Reiset  that  the  respiration  of  pure  oxygen  did  not  increase  the 
metabolism.  Licbig  was  convinced  that  atmospheric  pressure 
was  without  infiucncc,  for  it  was  evident  to  him  that  life  at  the 
sea-level  was  of  the  same  character  as  on  high  mountains.     In 

253 


254  SCIENCE    OF   NUTRITION. 

confirmation  of  these  principles  Zuntz^  has  recently  shown  that 
if  air  rich  in  oxygen  be  respired,  there  is  an  increased  oxygen 
absorption  lasting  for  about  one  minute,  and  then  the  normal 
quantity  is  absorbed.  The  primary  increase  in  the  quantity 
of  oxygen  absorbed  is  due  to  the  filling  of  the  lungs  with  oxygen 
and  a  further  saturation  of  the  blood  with  it,  processes  which 
are  without  effect  on  tissue  metabolism.  There  is  apparently 
no  retention  of  such  oxygen  within  the  cells  of  the  organism. 

However  Hill  and  Flack^  show  that  in  the  fatigue  of  athletes 
oxygen  inhalation  increases  the  lasting  power  and  decreases  the 
fatigue,  probably  by  maintaining  or  restoring  the  vigor  of  the 
heart.  They  believe  that  the  fatigue  which  follows  an  athletic 
feat  is  mainly  cardiac  in  origin,  and  due  to  want  of  oxygen. 

Pfiiiger^  first  showed  that  frogs  could  live  for  a  long  period  in 
an  atmosphere  which  was  free  from  oxygen  when  they  were 
maintained  at  a  temperature  of  o°.  After  five  hours  they  were 
capable  of  movement,  and  after  seventeen  hours  although 
apparently  dead  they  could  be  revived  when  placed  in  the  air. 
Fletcher  and  Hopkins*  have  found  traces  of  lactic  acid  in  normal 
resting  frogs'  muscle,  and  also  traces  after  a  series  of  muscular 
contractions  which  were  induced  in  an  atmosphere  of  oxygen; 
but  they  found  lactic  acid  in  large  quantity  in  the  muscle  if 
the  contractions  were  brought  about  under  anaerobic  conditions. 

Lesser^  has  placed  frogs  in  an  ice  calorimeter  and  filled  the 
chamber  in  which  they  lived  first  with  air  and  then  with  hydro- 
gen. When  living  in  air  the  animals  produced  more  heat  and 
only  half  as  much  carbon-dioxid  as  they  did  when  they  lived  in 
hydrogen  gas.  In  the  air  each  milligram  of  carbon  dioxid 
exhaled  corresponded  to  a  production  of  4.5  small  calories;  in 
hydrogen,  to  only  1.6  calories.  Hence  the  processes  taking 
place  in  the  two  cases  could  not  have  been  the  same.     The 

^Zuntz:   "Archiv  fiir  Physiologic,"  1903,  Suppl.,  p.  492. 

^  Hill  and  Flack:    "Journal  of  Physiology,"  1909,  vol.  xxxviii,  p.  xxviii. 

^Pfliiger:   "Pfliiger's  Archiv,"  1875,  Bd.  x,  p.  313. 

*  Fletcher  and  Hopkins:    "Journal  of  Physiology,"  1907,  vol.  xxxv,  p.  247, 

^Lesser:    "Zeitschrift  fiir  Biologic,"  1908,  Bd.  H,  p.  287. 


METABOLISM    IN   ANEMIA,  ^55 

anaerobic  carbon  dioxid  production  could  not  have  been  at  the 
expense  of  ox}'gen  stored  in  the  tissues  of  the  frog  or  the  heat 
production  per  unit  of  carbon  dioxid  exhaled  would  have  been 
the  same  as  in  air,  instead  of  being  only  35  per  cent,  as  much. 
The  processes  involved  in  this  case  can  only  be  conjectured. 
It  has  already  been  stated  that  ascaris,  an  anaerobic  inhabitant 
of  the  intestine,  may  convert  glycogen  into  fatty  acid  with  the 
elimination  of  carbon  dioxid  and  the  evolution  of  heat.  (See  p. 
176.)  Similar  processes  might  take  place  in  the  anaerobic  frog. 
Also  a  certain  amount  of  energy  is  liberated  when  dextrose  is 
converted  into  lactic  acid,  which  equals  3.4  per  cent,  of  that 
contained  in  the  sugar.  According  to  Zuntz,^  any  anemic  con- 
dition which  results  in  the  production  of  lactic  acid  makes 
demands  on  the  glycogen  reserves  of  the  body,  so  that  sugar  may 
rise  abnormally  in  the  blood,  and  both  sugar  and  lactic  acid 
appear  in  the  urine. 

The  consideration  of  the  subject  of  subnormal  oxygen  supply 
may  be  taken  up  with  bloodletting,  which  produces  an  artificial 
anemia.  Bauer,^  in  Voit's  laboratory,  was  the  first  to  study  this 
systematically  and  found  that  the  immediate  result  of  blood- 
letting in  the  dog  was  an  increased  protein  metabolism,  but 
that  the  carbon  dioxid  elimination  was  unchanged.  Eighteen 
to  27  per  cent,  of  the  total  blood  in  the  body  was  removed  in 
these  experiments. 

Hawk  and  Gies^  confirm  the  reports  of  a  higher  protein 
metabolism  after  bloodletting. 

Finkler,*  in  Pfliiger's  laboratory,  withdrew  one-third  of  the 
total  blood  from  a  dog,  thereby  reducing  the  rapidity  of  blood- 
flow  in  the  femoral  artery  by  one-half,  and  yet  there  was  no 
change  in  the  quantity  of  oxygen  absorbed,  and  therefore  of  the 
quantity  of  the  carbon  dioxid  exhaled.     Finkler  noted,  however, 

•Zuntz:    "Die  Kraftleistung  des  Ticrkorpers,"  Festrcde,   1908,  p.   18. 

*  Bauer:   "Zcitschrift  fiir  Biologic,"  1872,  Bd.  viii,  p.  567. 

'  Hawk  and  Gies:  "American  Journal  of  Physiology,"  1904,  vol.  xi,  p.  226. 

*  Finkler:   "Pfliiger's  Archiv,"  1875,  Bd.  x,  p.  368. 


256  SCIENCE    OF   NUTRITION. 

that  the  quantity  of  oxygen  in  the  venous  blood  grew  constantly 
less  after  repeated  bleedings.  This  indicates  the  inter-relation 
between  the  oxygen,  supply  and  the  needs  of  the  tissues.  Under 
ordinary  circumstances  there  are  20  volumes  per  cent,  of  oxygen 
in  the  arterial  blood,  of  which  12  volumes  per  cent,  may  return 
as  an  unused  excess  to  the  right  heart.  Repeated  bleedings  by 
Finkler  reduced  this  percentage  in  venous  blood  from  11.80 
per  cent,  to  8.80,  4.06,  and  2.71  per  cent.  The  carbon  dioxid 
content  of  the  blood  remained  unchanged.  This  decrease  in 
the  oxygen  content  of  the  blood  may  stimulate  both  the  heart  and 
respiration  to  compensatory  activity,  although  nothing  resem- 
bling asphyxia  be  present.  While  the  total  heat  production  is  un- 
changed in  anemia  following  bloodletting  (except  as  influenced 
by  increased  cardiac  and  respiratory  activity),  still  it  is  evident 
from  the  diminution  of  oxygen  present  in  venous  blood  that 
there  would  not  be  a  sufficient  supply  of  oxygen  to  provide  for  a 
largely  increased  metabolism.  Hence  the  anemic  organism 
is  incapable  of  great  muscular  work  without  quick  exhaustion 
accompanied  by  rapid  respiration  and  heart-beat.  These  lat- 
ter are  further  efforts  of  compensation  for  the  decrease  in  the 
oxygen- carrying  elements  of  the  blood. 

After  bloodletting  of  any  considerable  magnitude,  lactic 
acid  and,  it  is  reported,  a  small  amount  of  sugar,  appear  in 
the  urine.  Thus  Araki^  found  lactic  acid  in  the  urine  of  rabbits 
which  had  been  bled.  He  also  found  lactic  acid  in  the  urine  of 
rabbits  which  had  been  exposed  to  the  action  of  rarefied  air, 
and  he  found  lactic  acid  and  dextrose  in  the  urine  of  animals 
the  oxygen-carrying  capacity  of  whose  blood  had  been  dimin- 
ished through  the  respiration  of  carbon  monoxid.  It  should  be 
noticed  in  passing  that  wherever  lactic  acid  is  formed  in  the 
organism  there  is  a  concomitant  rise  in  protein  metabolism. 
The  anemic  condition  may  possibly  influence  the  enzyme 
which  normally  breaks  up  lactic  acid,  so  that  its  metabolism  is 
not  effected.     Since  this  lactic  acid  is  a  derivative  of  dextrose^ 

^  Araki:   "Zeitschrift  fur  physiologische  Chernie,"  1894,  Bd.  xix,  p.  424. 


METABOLISM    IN   ANEMIA.  257 

its  non-combustion  may  raise  the  protein  metabolism  to  a  higher 
level,  just  as  is  the  case  when  sugar  remains  unburned  in  dia- 
betes. This^is_true  in  spite  of  the  fact  that  the  total  metabolism, 
as  represented  by  the  heat  of  combustion  of  protein  and  fat, 
remains  unaltered. 

Another  fact  which  has  been  observed  by  Lewinstein^  is 
that  when  rabbits  are  kept  in  a  bell-jar  at  a  barometric  pressure 
of  300  to  400  mm.  (corresponding  to  5000  to  7500  meters  above 
sea-level)  they  die  on  the  second  or  third  day  and  autopsy 
reveals  extreme  fatty  infiltration  of  heart,  liver,  kidney,  and  dia- 
phragm. These  animals  took  no  food.  The  cause  of  this  fatty 
change,  in  the  present  writer's  opinion,  was  the  lessened  com- 
bustion of  sugar  or  its  derivative,  lactic  acid,  which  always 
induces  an  abnormal  deposit  of  fat  in  any  sugar-hungry  cells 

(P-  304)- 

Kohler^  artificially  compressed  the  trachea  of  rabbits  by 
tying  a  lead  wire  around  it.  The  animals  recovered  from  the 
operation  and  lived  for  four  weeks  in  a  condition  of  dyspnea. 
Appetite,  weight,  urine,  and  body  temperature  remained  normal 
almost  until  the  end.  The  dyspnea  was  apparently  insufhcient 
to  affect  the  metabolism.  Increased  respiration  and  heart 
activity  were  effectual  efforts  at  compensation,  so  that  there 
was  no  lack  of  oxygen  in  the  animals.  However,  the  altered 
pressure  in  the  lungs  and  the  continued  dyspnea  brought  about 
a  condition  of  stasis  of  which  the  animal  died.  The  secondary 
alterations  were  acute  and  widespread,  and  were  hyperemia 
of  the  lungs,  vesicular  and  intralobular  emphysema  of  the  lungs, 
and  hypertrophy  of  both  sides  of  the  heart. 

Pettenkofer  and  Voit^  observed  the  metabolism  in  an  acute 
case  of  leukocythemia  of  four  years'  duration,  and  at  a  time 
four  months  before  the  death  of  the  patient.  There  was  one 
white  to  every  three  red  blood-corpuscles,  a  high  degree  of 

•Lewinstein:  "Pfliiger's  Archiv,"  1897,  Bd.  Ixv,  p.  278. 
'Kohler:  "Archiv  fur  exper.  Path.  u.  Phann.,"  1877,  Bd.  vii,  p.  i. 
*  Pettenkofer  and  Voit:   "Zcitschrift  fiir  Biologie,"  1869,  Bd.  v,  p.  319. 
17 


258  SCIENCE    OF   NUTRITION. 

anemia,  and  great  physical  weakness.  The  metabolism  was 
exactly  the  same  as  in  a  normal  resting  man  living  under  the 
same  dietary  conditions. 

In  emphysema  of  the  lungs  in  man,  determinations  by  Gep- 
pert  and  by  Speck^  have  shown  that  the  respiratory  exchange 
of  gases  was  entirely  within  normal  limits. 

It  is  evident  from  these  various  citations  that  the  general 
oxidation  of  the  body  is  normally  maintained  in  anemia  and  in 
pulmonary  disease,  provided  the  disturbances  are  not  of  ex- 
treme intensity. 

The  constantly  increasing  use  of  mountain  air  as  a  recuper- 
ative force  for  the  worn-out  individual  leads  to  the  inquiry 
whether  the  metabolism  at  high  altitudes  is  different  from  that 
at  the  sea  level.  For  knowledge  of  this  sort  we  are  principally 
indebted  to  Zuntz  and  his  pupils.  The  study  of  the  subject 
may  be  taken  up  by  using  three  different  methods :  First,  the  - 
pneumatic  cabinet;  second,  balloon  ascensions;  third,  mountain 
ascents. 

The  pressure  of  the  atmosphere  varies  with  the  height  from 
the  sea-level  as  appears  in  the  following  table: 


Altitude. 

Barometer 

tiETERS. 

Feet. 

Miles. 

IN  Mm.  Hg. 

O 

0 

0. 

760 

lOOO 

3,281 

0.6 

670 

2000 

6,562 

1.2 

592 

3000 

9,843 

1.9 

522 

4000 

I3>i24 

2-5 

460 

5000 

16,405 

3-1 

406 

6000 

19,686 

3-7 

358 

7000 

22,967 

4.4 

316 

8000 

26,248 

5-0 

297 

The  relative  composition  of  the  atmosphere  is  the  same  at 
all  distances  from  the  earth's  surface.  Durig  and  Zuntz^  find 
that  the  atmosphere  at  a  height  of  2900  meters  contains  carbon 
dioxid  0.03  per  cent.,  nitrogen  79.11  per  cent.,  and  oxygen  20.86 
per  cent.,  whereas,  at  an  altitude  of  4600  meters  it  contains 

^  Cited  by  Jaquet:   "Ergebnisse  der  Physiologic,"  1903,  Bd.  ii,  I,  p.  562. 
^  Durig  and  Zuntz:   "Archiv  fiir  Physiologic,"  1904,  Suppl.,  p.  421. 


METABOLISM   IN  ANEMIA.  259 

carbon  dioxid  0.03  per  cent.,  nitrogen  79.10  per  cent.,  oxygen 
20.87  per  cent.  These  are  values  practically  identical  with  each 
other  and  with  those  determined  at  sea-level. 

Fraenkel  and  Geppert^  placed  a  dog,  which  had  fasted  seven 
days,  under  the  influence  of  greatly  diminished  atmospheric 
pressure  and  found  an  increased  protein  metabolism  which  con- 
tinued on  the  second  and  third  days.  They  also  suspected 
the  presence  of  products  of  incomplete  combustion  in  the  urine. 
These  results  accord  with  Araki's  investigations. 

Von  Terray^  finds  no  change  in  the  respiratory  activity  of 
dogs  in  air  containing  between  87  and  10.5  per  cent,  of  oxygen. 
When  10.5  per  cent,  of  oxygen  is  present  an  increased  respira- 
tor}^ activity  commences.  With  5.25  per  cent,  of  oxygen  there 
is  every  indication  of  lack  of  oxygen  for  the  tissues,  and  the 
elimination  of  lactic  acid  in  the  urine  is  pronounced.  The  quan- 
tity of  lactic  acid  eliminated  was  greatest  after  the  respiration  of 
an  atmosphere  containing  3  per  cent,  of  oxygen.  The  quantities 
obtained  were  1.206,  1.860,  2.176,  2.300,  2.352,  2.663,  3.020,  and 
3.686  grams  of  lactic  acid  in  twenty-four  hours.  In  these  cases 
we  again  see  the  analog}^  of  the  metabolism  to  that  already 
cited  as  having  been  discovered  by  Araki  after  bloodletting  in 
rabbits. 

L.  Zuntz^  found  that  when  he  respired  in  a  pneumatic  cab- 
inet, at  an  atmospheric  pressure  of  448  mm.  of  mercury,  there 
was  no  change  in  his  respiratory  metabolism  as  compared  with 
the  normal.    The  results  may  be  tabulated  as  follows: 

Per  Cent.  O2  Respired  Per  Minute. 

IN  Air.  Pressure  in  Mm.  Hg.  O2  c.c.  CO2  in  c.c 

21  758  mm.  231.25  200.15 

12  448  mm.  238.7  213. 1 

This  latter  experiment  was  done  at  a  pressure  corresponding 
to  a  mountain  height  of  4500  meters.     He  also  showed  that 

'Fraenkel  and  Geppcrt:  "  Ucbcr  die  Wirkungcn  der  vcrdunnten  Luft," 
1883. 

*  Von  Tcrray:   "Pfluger's  Archiv,"  1896,  Bd.  Ixv,  p.  440. 
»Locwy  and  Zuntz:   "Pfluger's  Archiv,"  1897,  Bd.  Ixvi,  p.  477- 


26o  SCIENCE   OF  NUTRITION. 

variations  in  atmospheric  pressure  within  the  above  limits  had 
no  effect  on  the  metabolism  during  muscular  exercise. 

Von  Schrotter  and  Zuntz^  made  two  balloon  ascents  to 
heights  of  4560  and  5160  meters.  Zuntz  showed  an  increased 
oxygen  absorption  of  7  per  cent,  above  that  at  sea-level.  In 
the  case  of  Von  Schrotter  the  increase  was  slight,  except  during 
one  interval  of  shivering,  when  a  20  per  cent,  increase  was  re- 
corded. The  authors  attributed  the  slight  rise  in  the  metabolism 
to  the  increased  work  done  by  the  respiratory  muscles.  During 
the  higher  ascent  sugar  appeared  in  the  urine  of  Zuntz,  indicating 
incomplete  oxidation. 

A  research  of  Zuntz^  on  the  subject  of  mountaineering 
describes  how  he  and  Durig  ascended  to  the  Col  d'Olen  (2900 
meters),  and,  having  remained  there  for  a  week,  passed  upward 
to  a  hut  (4560  meters)  constructed  near  the  summit  of  Monte 
Rosa,  the  highest  mountain  of  the  Alps  after  Mont  Blanc. 
They  lived  in  this  hut  two  weeks  and  a  half.  The  height  of  the 
barometer  was  443  millimeters,  which  indicates  a  quantity  of 
oxygen  amounting  to  12.2  per  cent,  of  an  atmosphere.  On 
the  Col  d'Olen  there  was  no  increase  in  their  metabolism  when 
they  were  resting,  and  there  was  no  increase  in  the  requirement 
of  energy  necessary  to  accomplish  one  kilogrammeter  of  work. 
This  agrees  with  the  results  of  Biirgi  elsewhere  mentioned 
(p.  207).  At  the  higher  level,  near  the  summit  of  the  mountain, 
the  resting  metabolism  increased  at  once  and  permanently  to 
the  extent  of  15  per  cent.  Zuntz  during  a  former  sojourn  had 
noted  an  increase  of  44  per  cent,  in  his  metabolism  when  on  the 
mountain.  Exposure  to  the  sunlight  was  almost  without  effect 
on  the  metabolism.  The  increased  metabolism  was  not  due  to 
cold,  for  it  was  present  when  the  individual  was  in  a  warm  bed 
in  the  hut.  At  sea-level  the  energy  equivalent  of  three  kilo- 
grammeters  is  liberated  in  the  body  in  order  to  lift  one  kilogram 
of  body  substance  one  meter  high.     Here  on  the  snow-fields  of 

^  Von  Schrotter  and  Zuntz:   Ibid.,  1902,  Bd.  xcii,  p.  479. 

^  Durig  and  Zuntz:    "Archiv  fiir  Physiologic,"   1904,  Suppl.,  p.  417. 


METABOLISM   IN   ANEMIA.  261 

Monte  Rosa  Durig  required  the  equivalent  of  4.0  to  4.8,  Zuntz 
5.3  to  6.8  kilogrammeters  of  energy  to  accomplish  one  kilogram- 
meter  of  work.  This  agrees  with  a  former  experiment  of  Zuntz 
when  he  was  living  in  the  same  locality,  in  which  he  found 
the  increased  metabolism  necessary  to  effect  one  kilogrammeter 
of  work  in  climbing  was  70  per  cent,  above  the  requirement 
for  the  same  work  at  sea-level. 

That  L.  Zuntz  (see  p.  259)  found  no  increase  in  his  metab- 
olism, either  during  rest  or  work,  when  he  was  in  a  pneumatic 
cabinet  under  an  atmospheric  pressure  of  448  mm.,  is  explained 
by  Durig  and  Zuntz  as  due  to  the  short  length  of  the  experiment. 

Not  only  is  the  metabolism  necessary  to  accomplish  work 
greater  on  high  mountains  than  at  sea-level,  but  the  capacity 
for  work  is  greatly  reduced.  Schumburg^  found  that  he  could 
accomplish  a  maximum  of  999  kilogrammeters  of  work  in  one 
minute  in  Berlin,  619  when  on  the  Monte  Rosa  glacier,  and  only 
354  kilogrammeters  when  he  was  on  the  top  of  the  mountain. 
The  limit  of  work  on  Monte  Rosa  was  therefore  one-third  what 
could  be  accomplished  in  Berlin,  probably  on  account  of  the 
accumulation  of  imperfectly  oxidized  products  of  metabolism, 
which  reduces  the  muscular  power.^ 

Durig  and  Zuntz,  Mosso,  and  others,  have  found  their  res- 
piration to  be  distinctly  of  the  Cheyne-Stokes  character  after  a 
return  to  the  hut  subsequent  to  exercise  in  the  higher  Alps. 
They  found  that  when  they  were  on  Monte  Rosa  a  temporary 
oppression  resulted  if  their  respiration  was  partly  hindered, — as 
in  the  case  of  lacing  their  boots.  Also,  strict  attention  to  a 
definite  task  might  reduce  the  respiratory  activity  to  such  an 
extent  that  anemia  of  the  brain,  accompanied  by  dizziness, 
readily  ensued. 

Workman^  reports  that  normal  sleep  was  impossible  when 
camping  in  the  Himalayas  at  a  height  of  19,358  feet  (nearly 

'  Zuntz  and  Schumburg:   "Pfltigcr's  Archiv,"  1896,  Bd.  Ixiii,  p.  488. 
^  Lee:    Fatigue,  "The  Harvey  Lectures,"  1905-06,  p.  169. 
*  Workman:    "Bulletin  of  the  American  Geographical  Society,"  1905,  vol. 
xxxvii,  p.  671. 


262 


SCIENCE   Of  ISrUTRITION. 


6000  meters).  When  the  individuals  of  the  party  dozed  they 
were  awakened  gasping  for  breath.  Air  at  this  height  con- 
tains 10  per  cent,  of  oxygen. 

The  ventilation  of  the  lungs  of  Durig  and  Zuntz  while  at 
rest  at  different  altitudes  varied  as  follows : 


Respited  in  Liters  per  Minute. 


Zuntz. 
Actual. 


Zuntz. 

Reduced  to  760  Mm. 

Hg  and  0°  C. 


Durig. 

Reduced  to  760  Mm. 

Hg  and  0°  C. 


Sea-level 

Cold'Olen 

Monte  Rosa 


4.61-5.03 
5-97-6-36 
6.86-8.52 


4-I5-4-53 
3.99-4.16 
3.71-4.88 


5.00-5.63 
3.81-5.07 
4.05-4.60 


The  actual  amount  of  inspired  air  appears  to  be  about  the 
same  at  different  altitudes,  an  increased  volume  compensating 
for  increasing  rarefaction  of  the  atmosphere. 

The  atmosphere  in  which  one  lives  is  really  the  air  within 
the  alveoli  (Pfluger).  Durig  and  Zuntz  have  calculated  the  pres- 
sure of  oxygen  and  carbon  dioxid  within  their  alveoli  at  dift'erent 
levels,  and,  measured  in  terms  of  millimeters  of  mercury,  have 
found  them  to  be  as  follows : 

Pressures  in  Mm.  Hg. 

Zuntz  (of  Berlin;.  Durig  (of  Vienna). 

O2  CO2  O2  CO2 

At  home — rest 107  36  109  32 

At  home — ascending  walk 109  ;^;}  99  37 

On  Monte  Rosa — rest 57  21  53  24 

On  Monte  Rosa — horizontal  walk 60  17  55  21 

On  Monte  Rosa — ascending  walk 63  18  55  24 

It  is  evident  from  a  study  of  the  results  that  muscular  exer- 
cise in  all  these  localities  produces  an  increase  in  the  alveolar 
tension  of  oxygen  and  a  decrease  in  that  of  carbon  dioxid. 
This  is  brought  about  by  the  stimulation  of  respiration. 

It  will  be  interesting  to  examine  the  evidence  of  the  effect 
of  decreasing  oxygen  tension  on  the  capacity  of  the  blood  in  the 
lungs  to  absorb  oxygen.  The  usually  accepted  doctrine  that 
atmospheric  air,  shaken  with  blood,  will  practically  saturate 


METABOLISM   IN   ANEMIA.  263 

the  hemoglobin  present,  rests  upon  Hufner's  experiments  with 
carefully  prepared  solutions  of  hemoglobin.  Loewy  and  Zuntz/ 
however,  show  that  if  normal  blood  be  used  the  saturation  is 
89  per  cent,  at  the  most.  On  the  basis  of  this  newer  work, 
Durig  and  Zuntz^  have  calculated  the  saturation  of  the  hemo- 
globin within  the  blood  at  the  different  altitudes.  At  Berlin, 
oxygen  exerting  alveolar  pressures  of  113  and  103  mm.  would 
saturate  the  blood  in  the  lungs  to  the  extent  of  81.9  and  80.5  per 
cent.,  respectively.  On  jMonte  Rosa  alveolar  oxygen  at  pres- 
sures of  57.0  mm.  (Zuntz)  and  53.2  mm.  (Durig)  would  respec- 
tively cause  a  saturation  to  the  extent  of  69.5  and  68  per  cent. 
The  lowest  recorded  oxygen  pressure  in  the  alveoli  was  48.3 
mm.  (Durig),  which  corresponded  to  65.9  per  cent,  of  oxyhemo- 
globin, and  was  accompanied  by  severe  headache.  A  quick- 
ened heart-beat  produced  a  more  rapid  circulation  than  normal. 
The  experimenters  find  no  ground  for  believing  that  there  was 
at  any  time  any  real  oxygen  deficiency  in  any  of  the  important 
tissues  of  the  body.  They  consider  that  their  gradual  ascent 
from  sea-level  prevented  the  usual  disturbances  of  appetite  and 
digestion  which  are  probably  caused  by  anemia  in  the  abdominal 
region  (mountain  sickness). 

After  exercise,  however,  Zuntz  and  Durig  noted  qualitative 
changes  in  the  metabolism  indicating  incomplete  combustion. 
This  was  shown  in  the  reduction  of  the  respiratory  quotient 
below  that  of  fat.  The  authors  say:^  "The  experiments  leave 
no  doubt  that  the  increased  deficiency  of  oxygen  supply,  induced 
by  the  greater  metabolism  of  the  tissue  during  exercise,  is  asso- 
ciated with  the  cause  of  the  increased  requirement  of  energy." 

There  is  no  reference  to  the  presence  of  either  sugar  or  lactic 
acid  in  the  urine  after  exercise  on  Monte  Rosa,  substances 
whose   presence  one   might  suspect.     Loewy''  reports  an   in- 

'  Loewy  and  Zuntz:   "Archiv  fiir  Physiologic,"  1904,  p.  207. 

*  Durig  and  Zuntz:   Loc.  cit.,  p.  442. 

^  Autorcnrcfcrat:    "Biochemisches  Centralblatt,"  1904,  Bd.  iii,  p.  285. 

*  Loewy:    "Archiv  fiir  Physiologic,"  1906,  p.  386. 


264  SCIENCE   OF  NUTRITION. 

creased  excretion  of  amino-acids  during  mountain  sickness 
or  during  exercise  at  these  high  altitudes. 

It  is  apparent  that  hfe  at  an  altitude  of  4600  meters  is  on  the 
borderland  between  the  normal  and  the  dyspneic.  Less  work 
can  be  accomplished,  and  this  at  the  expense  of  a  greater  metab- 
olism, because  of  the  inhibition  of  the  muscle  mechanism 
through  the  accumulation  of  imperfectly  burned  products  of 
metabolism. 

Higher  mountain  ascents  have  been  accomplished  than  the 
one  here  described.  The  celebrated  mountaineer,  Whymper, 
has  ascended  Chimborazo  (6247  meters)  without  suffering 
from  mountain  sickness. 

Boycott  and  Haldane^  found  in  experiments  on  themselves 
when  they  were  confined  in  a  steel  pneumatic  cabinet  that  if  the 
atmospheric  pressure  was  reduced  to  356  mm.  of  mercury, 
corresponding  to  a  height  of  6000  meters,  the  oxygen  pressure 
in  the  alveoli  feU  to  30  mm.  and  pronounced  cyanosis  occurrec, 
accompanied  first  by  loss  of  memory  and  then  by  unconscious- 
ness. There  was  only  slight  hyperpnea.  Greater  attenuation 
of  the  atmosphere  on  mountains  and  in  balloons  may  often  be 
tolerated.  This  they  ascribe  to  a  gradual  production  of  lactic 
acid  within  the  organism  which  renders  the  respiratory  center 
especially  sensitive  to  the  stimulus  of  carbon  dioxid.  They 
recommend  that  one  frequently  partake  of  carbohydrates  when 
among  the  higher  mountains  in  order  that  a  maximum  amount 
of  carbon  dioxid  be  furnished  to  the  blood  stream.  The  carbon 
dioxid  pressure  in  the  alveoli  falls  as  an  accompaniment  of  the 
rising  acid  content  of  the  body.  This  changed  condition  of  the 
blood  does  not  pass  off  at  once  on  return  to  a  lower  level  •?  The 
respiratory  stimulus  persists  and  the  beneficial  effects  of  descend- 
ing are  promptly  felt.  At  a  given  altitude  on  the  descent  the 
alveolar  oxygen  pressure  will  therefore  probably  be  higher  than 

^Boycott  and  Haldane:  "Journal  of  Physiology,"  1908,  vol.  xxxvii, 
p.  262. 

2  Ward:  Ihii.,  p.  378. 


METABOLISM   IN   ANEMIA. 


265 


at  the  same  altitude  on  the  ascent  on  account  of  the  greater 
stimulation  of  the  respiratory  center. 

These  relations  are  shown  in  the  following  table  compiled 
from  Ward's  experiments  on  himself: 


Pressures  in  Mm.  of  Hg. 

Barometer. 

Alveolar  Air. 

CO2. 

O2. 

Lister  Institute,  London 

769 
633 
443 
633 

37-7 
34-2 
28.5 
28.9 
32-5 

109.0 
81.6 
49.8 
91.0 

Zermatt 

Monte  Rosa 

Zermatt,  on  return 

2  hours  after 

One  may  compare  the  statement  of  Boycott  and  Haldane  that 
cyanosis  occurred  in  them  when  the  oxygen  pressure  in  the 
alveoli  fell  to  30  mm.  with  the  statement  of  Loewy  and  Zuntz^ 
that  when  the  oxygen  pressure  is  31.8  human  blood  will  absorb 
oxygen  so  that  56  per  cent,  of  its  hemoglobin  is  saturated.  This 
agrees  well  with  the  finding  of  Ringer^  in  the  author's  laboratory 
that  dogs  lose  consciousness  when  their  hemoglobin  becomes  half 
saturated  with  carbon  monoxid  gas.  Ringer's  dogs,  however, 
were  not  beyond  the  power  of  resuscitation  until  70  per  cent,  of 
the  hemoglobin  was  combined  with  the  poisonous  gas. 

This  observation  is  similar  to  that  of  Bornstein  and  Miiller,^ 
who  have  shown  that  death  occurs  when  70  per  cent,  of  the 
hemoglobin  of  the  blood  is  converted  into  methemoglobin  by 
magnesium  chlorid.  Rapid  recovery  takes  place  if  the  process 
is  not  carried  so  far  as  this. 

New  and  striking  experiments  by  Rosendahl*  in  Kronecker's 
laboratory  indicate  that  if  the  atmospheric  pressure  be  reduced 

*  Loewy  and  Zuntz:    "Archiv  fiir  Physiologic,"  1904,  p.  214. 

*  Ringer:   Unpublished. 

'  Bornstein  and  Miiller:    "Archiv  fiir  Physiologie,"  1907,  p.  470. 
*Rosendahl:    "Zeilschrift  fur  Biologic,"  1908,  Bd.  lii,  p.  16. 


266  SCIENCE   OF   NUTRITION. 

to  such  an  extent  as  to  produce  respiratory  distress  in  rats  and 
rabbits,  and  then  pure  nitrogen  gas  be  admitted,  the  symptoms 
of  suffocation  disappear.  From  this  he  concludes  that  diminished 
atmospheric  pressure  disturbs  the  mechanics  of  blood  circulation 
through  the  lungs,  and  that  dyspnea  in  rarefied  air  is  not 
primarily  caused  by  lack  of  oxygen  in  the  atmosphere. 

Tolerance  for  the  highest  altitudes  depends  on  individual 
idiosyncrasy,  which  has  been  variously  attributed  to  differences 
in  the  capacity  of  hemoglobin  to  absorb  oxygen,  to  differences 
of  diffusion  power  in  the  alveolar  membrane,  and  to  suscepti- 
bility to  cosmic  influences,  such  as  electric  and  magnetic  phe- 
nomena. Or  it  may  be  due  to  the  ability  of  the  organism  to 
react  so  that  acid  products  accumulate  which  sensitize  the  res- 
piratory center  as  Ward's  experiments  suggest. 

'  The  discovery  of  Viault^  that  at  an  altitude  of  4000  meters 
the  number  of  red  blood-cells  increased  to  7,000,000  and 
8,000,000  per  cubic  mm.  of  blood  appeared  at  first  to  indicate 
a  compensatory  increase  in  oxygen-combining  power  during 
life  in  rarefied  air.  However,  Abderhalden^  has  shown  that 
this  phenomenon  is  due  to  an  expression  of  blood  fluid  from  the 
circulatory  system  and  a  consequent  thickening  of  the  blood, 
for  he  finds  no  change  in  the  total  quantity  of  hemoglobin  in 
animals  of  the  same  species  when  they  are  killed  at  different 
heights.  Only  after  prolonged  residence  at  a  high  altitude  may 
any  increase  in  the  quantity  of  hemoglobin  be  possible.^  Such 
an  increase  has  been  positively  shown  by  Zuntz  and  his  co- 
workers.* 

The  results  of  these  varied  experiments  confirm  the  inde- 
pendence of  the  metabolism  of  variations  in  atmospheric  pres- 
sure as  regards  all  the  customary  habitats  of  mankind.     The 


^  Viault:  "  Comptes  rendus  de  I'academie  des  sciences,"  1890,  T.  cxi,  p.  917. 
^  Abderhalden:   "Zeitschrift  fiir  Biologic,"  1902,  Bd.  xliii,  p.  443. 
^  Abderhalden:    "Pfliiger's  Archiv,"  1905,  Bd.  ex,  p.  98. 
*  Zuntz,  Loewy,  Miiller,  and  Caspari:  "Hohenklima  und  Bergwanderungen 
in  ihrer  Wirkung  auf  den  Menschen,"  Berlin,  1906. 


METABOLISM    IN   OBESITY,  267 

beneficial  properties  of  mountain  air  may  be  largely  the  same 
as  those  derived  at  watering-places,  i.  e.,  outdoor  life,  cool  air, 
exercise,  diversion  through  change  of  scene,  mental  rest,  and, 
finally,  suggestion  of  benefits  received.  The  dry,  crisp 
air  undoubtedly  benefits  catarrhal  disturbances,  which  are, 
on  the  other  hand,  aggravated  by  the  climate  of  the  sea- 
shore. 

In  the  search  for  conditions  which  might  reduce  the  intensity 
of  metabolism,  the  infliuence  of  the  internal  secretions  of  the 
sexual  glands  has  been  prominently  considered.  Careful 
experiments  of  Luthje,^  however,  show  that  castration  in  dogs 
of  both  sexes  has  no  influence  on  the  metabolism.  It  is  said, 
however,  that  removal  of  the  ovaries  reduces  for  a  time  the 
number  of  red  blood-corpuscles,  and  it  is  suggested  that  ovarian 
insufficiency  may  be  the  cause  of  chlorosis.^ 

Von  Bergmann^  has  shown  that  although  many  cases  of 
normal  metabolism  in  obesity  have  been  recorded  (see  p.  170), 
he  has  been  able  to  establish  the  fact  that  in  some  cases  there  is 
a  constitutional  reduction  in  the  intensity  of  the  metabolic 
processes.  Thus  he  found  at  certain  times  in  two  obese  in- 
dividuals a  normal  metabolism,  which  was  measured  by  a  heat 
production  of  2100  and  2300  calories  and  by  an  excretion  of 
respiratory  carbon  equal  to  180  and  190  grams  daily.  At  other 
times  in  these  same  individuals  the  metabolism  was  found  to 
have  reached  the  low  values  of  1500  and  1780  calories  (695  to 
662  calories  per  square  meter  of  surface),  while  the  expired 
carbon  measured  124  and  138  grams.  These  are  the  first 
experiments  which  establish  the  existence  of  a  true  reduction 
in  the  metabolism  of  obese  individuals.  The  predisposition 
to  obesity  may  be  due  to  deficient  thyroid  secretion. 

*  Liithje:   "  Archiv  fiir  ex.  Path,  und  Pharm.,"  1902,  Bd.  xlviii,  p.  184 
'  Breucrand  v.  Seiller:  "Arch.  f.  ex.  Path,  und  Pharm.,"  1903,  Bd.  1,  p.  169. 
'Von  Bcrgmann:  "Zeitschift  fiir  ex.  Path,  und  Therapie,"   1909,  Bd.  v, 
p.  646. 


268  SCIENCE   OF   NUTRITION. 

The  thyroid  gland  is  a  gland  whose  internal  secretion 
profoundly  affects  the  amount  of  general  metabolism.  This 
influence  is  apparently  brought  about  by  a  substance  called 
thyroidin,  which,  when  produced  in  normal  quantities,  main- 
tains the  proper  functions  of  the  nervous  system.  A  subnormal 
production  reduces  the  activity  of  the  nervous  system  and  in- 
cidentally the  quantity  of  metabolism.  An  over-production 
increases  the  irritability  of  the  nervous  apparatus  and  raises 
the  metabolism.  Myxedema  is  a  condition  in  which  the  thy- 
roid gland  has  atrophied  and  its  secretion  is  no  longer  available. 
Exophthalmic  goiter  presents  the  opposite  phase,  since  here  a 
superabundance  of  thyroidin  is  believed  to  be  produced.  Symp- 
toms somewhat  akin  to  the  latter  condition  may  be  induced  by 
ingesting  thyroid  extracts  in  normal  animals  and  man. 

Magnus-Levy^  found  the  carbon  dioxid  output  increased 
after  giving  a  normal  man  thyroid  extracts.  Fritz  Voit^  finds 
the  same  to  be  true  of  a  dog,  and  also  that  more  protein  is  metab- 
olized. It  is  this  latter  action  which  contraindicates  thyroid 
feeding  in  obesity.  However,  Rheinboldt^  states  that  a  man 
fed  with  thyroid  extracts  may  be  maintained  in  nitrogen  equi- 
librium if  much  protein  be  allowed  in  the  diet. 

Anderson  and  Bergman*  have  given  large  quantities  of  thy- 
roid extract  to  a  man  who  was  kept  in  perfect  quiet,  and  no 
increased  output  of  carbonic  acid  was  noticed.  They  attribute 
the  increased  metabolism  which  is  usually  observed  to  the 
increased  muscle  tonus  caused  by  the  highly  irritated  central 
nervous  system.  A  high  metabolism  is  observed  in  cases  of 
exophthalmic  goiter.  Freidrich  Miiller^  reports  a  case  of  an 
individual  weighing  only  29  kilograms  who  constantly  lost 
weight  notwithstanding  a  daily  diet  containing  68  grams  of 

1  Magnus-Levy:  "Berliner  klinische  Wochenschrift,"  1895,  Bd.  xxx,  p.  650. 

^  Voit,  F.:   "Zeitschrift  fiir  Biologie,"  1897,  Bd.  xxxv,  p.  116. 

^  Rheinboldt:   "Zeitschrift  fiir  klin.  Med.,"  1906,  Bd.  Iviii,  p.  425. 

^Anderson  and  Bergman:  "Skan.  Archiv  fiir  Physiologie,"  1898,  Bd.  viii, 
p.  326. 

^  Miiller:   "Deutsches  Archiv  fiir  klin.  Medizin.,"  Bd.  li,  p.  361. 


METABOLISM   IN   EXOPHTHALMIC    GOITER. 


269 


protein  with  58  calories  per  kilogram.  Under  such  circum- 
stances there  is  undoubtedly  an  abnormally  high  destruction  of 
both  protein  and  fat.  The  increased  protein  destruction  has 
been  attributed  to  toxic  influence  of  the  thyroid  secretion. 
It  may,  however,  be  caused  by  an  overheating  of  the  muscle  cells 
due  to  great  heat  production.  Magnus-Levy^  finds  an  increased 
oxygen  intake  in  cases  of  exophthalmic  goiter  amounting  to 
22,  42,  and  70  per  cent,  above  the  normal. 

Steyrer^  has  made  the  first  complete  experiments  on  the 
metabolism  in  this  disease.  The  patient  was  twenty-one  years 
old,  temperature  normal;  the  total  metabolism  during  two  days 
was  determined  twice  at  intervals  one  month  apart  and  while 
the  person  was  resting  in  bed.  During  the  second  period  the 
disease  had  made  considerable  progress,  the  patient  having 
a  hot  skin  and  being  in  a  highly  nervous  state. 


Period  I 

Period  II  (one  month  later) 


Day. 


/I 

l2 


Calories  of 

Metabolism. 


2665 

2731 
3666 

3318 


Weight 
IN  Kg. 


45-1 
46.4 
48.2 
47-5 


Calories 
PER  Kg. 


59-1 
5S.9 
76.1 
69.9 


In  myxedema  the  metabolism  is  reduced  and  there  is  a  fall  in 
body  temperature.  Anderson^  reports  a  case  of  a  woman  whose 
metabolism  was  as  low  as  1260  calories  or  18.8  per  kilogram: 
after  treatment  for  nine  months  with  thyroid  extracets  the  hat 
production  rose  to  2099  calories,  or  32.3  per  kilogram.  These 
latter  are  normal  values.  The  temperature  rose  with  the  in- 
crease in  metabolism. 

It  is  possible  to  explain  the  reduced  temperature  as  due  to 
disturbances  in  the  nerve  mechanism  of  temperature  regulation. 

'Magnus-Levy:  von  Noorden's  "Handbuch  der  Pathologic  des  Stoff- 
wechsels,"  1907,  p.  325. 

^  Steyrcr:   "Zeilschrift  f.  exp.  Path,  und  Therapie,"  1907,  Bd.  iv,  p.  720. 

*  Anderson:  "Hygeia,"  Stockholm,  1898  (quoted  in  Tigerstedt's  "Lehrbuch 
der  Physiologic"). 


270  SCIENCE   OF  NUTRITIOIS. 

The  diminished  temperature  of  the  body  would  then  be  an 
influence  in  reducing  the  metabolism  of  the  cells.  This  disease 
is  a  rare  example  of  a  condition  in  which  the  metabolic  processes 
are  permanently  depressed. 

Clonic  convulsions  are  a  symptom  following  parathyroidec- 
tomy, and  during  these  periods  the  temperature  rises.  Mac- 
Callum^  reports  that  the  temperature  of  a  dog  in  which  after 
parathyroidectomy  violent  tetany  developed,  rose  from  39° 
to  43.2°  during  the  attack.  The  administration  of  calcium 
acetate  stopped  the  convulsions  in  a  few  minutes  and  within 
half  an  hour  the  temperature  fell  to  38.9°. 

^  MacCallum:  Fever,  Harvey  Society  Lecture,  "Archives  of  Internal  Medi 
cine,"  1908,  vol.  ii,  p.  572. 


CHAPTER  XII. 

METABOLISM   IN   DIABETES   AND   IN   PHOSPHORUS- 
POISONING. 

It  is  said  that  the  sweet  taste  of  diabetic  urine  was  familiar  to 
Susruta,  a  physician  who  lived  in  India  during  the  seventh  cen- 
tury. The  disease,  then  as  now,  may  have  been  more  prevalent 
among  the  Hindoos  than  elsewhere  in  the  world.  In  Europe 
the  sweet  taste  of  diabetic  urine  was  discovered  by  Thomas 
Willis  in  1674,  but  it  was  not  till  after  another  hundred  years 
that  Dobson,  in  1775,  showed  that  the  taste  was  due  to  the 
presence  of  sugar.  Subsequently  the  coexistence  of  a  hyper- 
glycemia was  established. 

Claude  Bernard  found  that  the  stimulation  by  puncture  of 
a  group  of  cells  (the  "diabetic  center")  lying  in  the  medulla  near 
the  floor  of  the  fourth  ventricle,  gave  rise  to  an  excretion  of 
sugar  in  the  urine.  This  experiment  is  the  source  of  the  false 
impression  that  diabetes  is  essentially  of  nervous  origin.  It  is 
called  la  piqilre. 

Diabetes  is  a  disease  of  particular  interest,  since  it  is  a  depart- 
ure from  the  physiological  condition  involving  the  capacity  of 
the  organism  to  care  for  sugar  in  the  normal  fashion.  All  the 
symptoms  are  due  to  this  one  fact.  No  other  disease  has  been 
more  thoroughly  investigated.  The  study  of  diabetes  has 
wonderfully  developed  a  knowledge  of  the  intermediary  meta- 
bolism of  protein,  fat,  and  carbohydrates.  In  presenting  the 
details  to  the  reader,  it  may  be  remarked  that  the  work  done  is 
prophetic  of  possible  accomplishment  along  scientific  lines  in 
the  study  of  disease.  It  is  typical  of  that  "scientific  medicine" 
which  affrights  the  spirits  devoted  to  a  passing  empiricism. 

The  foundation  of  modern  knowledge  on  this  subject  was 

271 


272  SCIENCE   OF  NUTRITION. 

laid  by  von  Mering  and  Minkowski^  and  by  Minkowski  alone, 
who  extirpated  the  pancreas  in  dogs  and  demonstrated  that 
such  animals  became  diabetic. 

The  causes  of  the  appearance  of  sugar  in  the  urine  are: 
(i)  Either  the  organism  cannot  burn  sugar,  which  therefore 
accumulates  in  the  blood  in  excess  of  the  normal,  and  is  filtered 
through  the  kidney  (diabetes  mellitus,  experimental  pancreas 
diabetes);  or  (2)  some  tissues  may  lose  their  sugar-retaining 
function  so  that  the  normal  regulatory  control  of  the  quantity 
of  blood-sugar  is  lost  or  diminished  (Bernard's  piqtire,  ali- 
mentary glycosuria,  phlorhizin  glycosuria). 

The  stimulation  of  Bernard's  "diabetic  center"  is  effective 
in  its  results  only  when  the  liver  contains  glycogen.^  This 
form  of  glycosuria  cannot  be  obtained  in  a  starving  animal.  It 
is  attributed  to  a  sudden  flushing  of  the  liver  with  blood  and  a 
conversion  of  glycogen  into  sugar,  so  that  hyperglycemia  and 
sugar  elimination  through  the  kidney  follow. 

Alimentary  glycosuria  is  seen  in  normal  animals  and  in  man, 
when  sugar  is  given  in  larger  quantities  than  the  glycogen  regu- 
latory function  can  care  for.  Moritz*  found  two  grams  of 
dextrose  in  the  urine  of  a  man  after  the  ingestion  of  200  grams. 
Such  an  alimentary  glycosuria  lasts  between  three  and  six  hours. 

Hofmeister^  has  discovered  that  the  fasting  organism  is  more 
susceptible  to  alimentary  glycosuria  than  the  well-fed  one. 
He  calls  such  a  condition  "starvation  diabetes."  Evidently  an 
organism  whose  glycogenic  function  has  not  been  used  is  less 
capable  of  protecting  itself  from  an  excess  of  dextrose  than  it  is 
during  normal  nutrition. 

Moritz^  observed  0.2  to  0.3  per  cent,  of  sugar  in  the  urine  of 

^  Von  Mering  and  Minkowski:  "Archiv  fiir  ex.  Path,  und  Phann.,"  1889, 
Bd.  xxvi,  p.  371. 

^  Minkowski:   Ihid.,  1893,  Bd.  xxxi,  p.  85. 

^  Dock:   "Piluger's  Archiv,"  1872,  Bd.  v,  p.  571. 

^jMoritz:  " Verhandlungen  des  10  Congresses  fiir  innere  Medizin/'  1891, 
p.  492. 

^  Hofmeister:  "Archiv  fiir  ex.  Path,  und  Pharm.,"  1890,  Bd.  xxvi,  p.  355. 

'Moritz:   "Archiv  fiir  klinische  Medizin,"  1890,  Bd.  xlvi,  p.  217. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.    273 

four  out  of  six  healthy  people  who  had  partaken  of  a  quantity 
of  sweets  and  champagne. 

Evidently  such  conditions  as  these  are  not  to  be  classed  with 
diabetes  mellitus,  where  there  is  a  fundamental  disturbance  in 
the  sugar-burning  power  in  the  organism.  It  would  be  of  ser- 
vice to  distinguish  between  glycosurias  where  the  sugar-holding 
capacity  of  the  organs  has  been  diminished  or  overstrained,  and 
diabetes  in  which  the  sugar-burning  capacity  has  been  affected. 

A  special  type  of  glycosuria  is  caused  by  phlorhizin  injec- 
tions, as  was  discovered  by  von  Mering.^  Here  the  blood  itself 
while  passing  through  the  kidney  loses  the  power  of  retaining 
its  normal  sugar  content  and  a  hypoglycemia  results.  Some- 
times when  the  kidney  is  altered  in  B right's  disease,  phlor- 
hizin is  ineffective  and  no  glycosuria  follows  its  administration. 
The  renal  character  of  phlorhizin  glycosuria  was  demonstrated 
by  Zuntz,^  who  placed  cannulae  in  the  upper  portions  of  the  two 
kidneys  and  injected  phlorhizin  into  the  renal  artery  of  one. 
On  the  injected  side,  sugar-containing  urine  appeared  in  two 
minutes,  and  three  minutes  later  the  kidney  on  the  opposite 
side  yielded  sugar  through  its  ureter.  The  delay  was  due  to  the 
lapse  of  time  necessary  for  the  transportation  of  the  phlorhizin 
by  the  blood  stream  from  the  injected  kidney  to  the  other  one. 
In  this  form  of  glycosuria  sugar  ingested  per  os,  or  subcutane- 
ously,  or  as  formed  in  protein  metabolism,  is  all  eliminated  in 
the  urine,  provided  the  quantity  given  does  not  flood  the  organ- 
ism with  sugar.^    In  this  latter  case  part  of  it  can  be  burned. 

Loewi*  has  conceived  the  idea  that  the  blood  sugar  is  nor- 
mally in  a  loose  combination  with  colloid  substance.  This 
colloid-sugar  cannot  pass  through  the  glomerulus.  If,  how- 
ever, sugar  accumulates  in  the  blood  above  the  combining  power 
of  the  colloid,  then  the  crystalloid  dextrose  readily  passes  away 

'  Von  Mering:  "Verhandlungen  des  5  Congresses  fiir  innere  Medizin," 
1886,  p.  185. 

*Zuntz:   "  Archiv  fiir  Physiologic,"  1895,  p.  570. 

'  Stiles  and  Lusk:  "American  Journal  of  Physiology,"  1903,  vol.  x,  p.  67. 
*  Loewi:  "  Archiv  fiir  ex.  Path,  und  Pharm.,"  1902,  Bd.  xlviii,  p.  410. 
18 


274  SCIENCE   OF  NUTRITION. 

through  the  kidney.  This  condition  exists  in  diabetes  melHtus. 
In  phlorhizin  glycosuria  the  kidneys  break  up  the  colloid  sugar, 
and  the  sugar  may  then  be  eliminated.  Stiles  and  Lusk,  while 
accepting  Loewi's  theory,  have  added  the  hypothesis  that  the 
colloid  sugar  cannot  be  burned.  Phlorhizin  acting  in  the  kid- 
ney will  split  the  compound  and  permit  the  elimination  of  sugar. 
Any  free  dextrose  in  the  general  circulation  unites  with  the 
colloid  radical  and  is  protected  from  combustion,  as  is  the  case 
when  five  grams  of  dextrose  are  administered  subcutaneously, 
only  to  reappear  in  the  urine  (Stiles  and  Lusk).  If  the  quantity 
of  sugar  in  the  blood  rises  above  this  combining  power,  immunity 
from  destruction  is  lost  and  the  sugar  burns.  The  presence  of 
a  colloid-dextrose  combination  is  denied  by  Rosenfeld  and  Asher,^ 
who  find  that  the  sugar  of  normal  blood  is  readily  diffusible. 

Phlorhizin  glycosuria  is  only  temporary  in  character,  and 
subcutaneous  injections  of  alkaline  solutions  of  the  drug  three 
or  four  times  daily  are  necessary  in  order  to  obtain  constant 
results.  The  character  of  phlorhizin  glycosuria  has  been 
dwelt  upon  because  the  total  metabolism  is  here  identical  with 
that  observed  in  diabetes  mellitus. 

Von  Mering  and  Minkowski^  removed  the  pancreas  from  dogs 
and  obtained  a  condition  which  was  markedly  analogous  to 
diabetes  mellitus  in  man.  There  is  hyperglycemia  and  a  large 
excretion  of  dextrose  in  the  urine;  ingested  dextrose  can  not  be 
burned,  but  is  completely  eliminated.  The  dogs  show  a 
considerable  acidosis,  with  excretion  of  ^-oxybutyric  acid,  and 
they  die  in  coma.^  If  a  portion  of  the  gland  remain  in  the 
abdominal  cavity  there  is  either  no  diabetes  or  only  a  partial 
diabetes.  If  a  portion  of  a  pancreas  be  transplanted  into  the 
abdominal  cavity  of  a  depancreatized  dog,  the  diabetes  is  stopped 
or  reduced  as  long  as  the  transplanted  piece  remains  functional. 

^  Rosenfeld  and  Asher:  " Zentralblatt  fiir  Physiologie,"  1905,  Bd.  xix, 
p.  449. 

^Von  Mering  and  Minkowski:  "Arch.  f.  exper.  Path.  u.  Pharmakol.," 
1889,  Bd.  xxvi,  p.  371. 

^  AUard:   "Arch.  f.  exper.  Path,  und  Pharmakol.,"  1908,  Bd.  lix,  p.  391. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.   275 

Such  experiments  as  have  been  made  in  man  have  not  been 
successful.  Minkowski^  reports  that  if  a  piece  of  the  pancreas 
be  ingrafted  under  the  skin  of  a  dog  and  afterward  the  whole 
of  the  remainder  of  the  pancreas  be  removed  from  the  abdomen, 
the  dog's  urine  remains  free  from  sugar  for  two  months,  but 
on  extirpation  of  the  piece  ingrafted  under  the  skin  an  extreme 
diabetes  sets  in. 

It  has  long  been  knowTi  that  diabetics  eliminate  sugar  even 
after  all  administration  of  sugar  is  stopped.  It  has  also  been 
generally  recognized  that  protein  ingestion  tends  to  increase 
the  sugar  output  in  the  urine,  w^hile  fat  has  no  effect. 

A  large  amount  of  information  has  been  collected  concerning 
the  relation  between  the  urinary  nitrogen  and  sugar  elimination 
in  the  fasting  and  meat-fed  diabetic  organism.  The  dextrose 
to  nitrogen  ratio  (D  :  N)  is  a  key  to  the  problem  of  the  quantity 
of  sugar  which  can  be  derived  from  protein  metabolism  (p.  132). 

Minkowski^  was  the  pioneer  who  discovered  that  depan- 
creatized  dogs,  whether  fasting  or  fed  with  meat,  showed  a  con- 
stant elimination  of  2.8  grams  of  dextrose  for  each  gram  of  ni- 
trogen in  the  urine.  This  ratio  (D  :  N  ::  2.8  :  i)  was  the 
average  obtained  from  seven  dogs  on  twenty-two  different  days. 
The  lowest  ratio  was  2.62  :  i,  the  highest  3.05  :  i.  Some  other 
operators  have  been  unable  to  obtain  these  ratios.  Pfliiger^ 
finds  a  variable  and  generally  lower  ratio,  and  his  dogs  all  died 
of  abscesses.  Embden's*  ratios  are  all  lower  than  Minkowski's, 
and  are  probably  due  to  incomplete  extirpation  of  the  pancreas. 

The  accuracy  of  Minkowski's  results  is  indicated  by  the  fact 
that  the  ratio  (D  :  N  :  :  2.8  :  i)  may  be  easily  established  by  the 
administration  of  phlorhizin  to  rabbits,  goats,  cats,  and  in  cer- 
tain dogs  whose  kidneys  have  been  somewhat  affected,  as,  for 

'  Minkowski:  "Arch.  f.  expcr.  Path.  u.  Pharmakol.,"  1908,  Supplementband, 
P-  399- 

'  Minkowski:   "Archiv  fiir  ex.  Path,  unci  Pharm.,"  1893,  Bd.  xxxi,  pp.  85, 

97- 

*  Pfliiger:   "Das  Glycogen,"  1905,  p.  491. 

*Embden  and  Salomon:   " Ilof meisler's  Beitrage,"  1904,  Bd.  vi,  p.  63. 


276 


SCIENCE   OF  ZSrUTRITION. 


example,  by  giving  camphor.  Phlorhizin  acts  first  to  cause  a 
sweeping  out  of  the  excess  of  sugar  in  the  organism,  with  a  sub- 
sequent establishment  of  the  ratio.  (See  table,  p.  285.)  The 
ratios  in  different  animals  are  given  in  the  following  table: 


RATIOS  IN  DIABETES  OF  D   :  N 


2.8 


DOG.I 

D0G.2 

CaT.3 

Goat.* 

Rabbit.5 

Day. 

£5 

1   s 
g  6 

1 

d 

■-a 

1 
0 

Ph 

Second  day  of  Diabetes 

Third       "             "           

Fourth     "             "           

Fifth        "             "           

Day  unknown 

2^88 
2.94 
3-09 

2.8 

2-93 

2.80 

2-93 

2-95 
2.90 
2.78 

2.89 
2.69 

The  uniformity  of  the  ratio  as  shown  in  different  animals  is 
very  striking.  One  may  calculate  from  these  results  that  45 
per  cent,  of  the  protein  molecule  may  be  converted  into  dex- 
trose in  the  course  of  metabolism. 

This,  however,  does  not  complete  the  story  of  the  D  :  N 
ratio,  for  a  higher  ratio,  or  3.75  :  i,  was  discovered  by  Reilly, 
Nolan,  and  Lusk^  in  the  urine  of  dogs  with  normal  kidneys, 
after  subcutaneous  injections  of  phlorhizin.  This  ratio  was 
subsequently  revised  by  Stiles  and  Lusk^  and  found  to  be 
3.65  :  I.  The  importance  of  this  discovery  was  enhanced  by 
the  finding  of  Mandel  and  Lusk^  that  the  same  ratio  may  exist 

^  Minkowski:   Loc.  cit.,  p.  97. 

^  Jackson:   "American  Journal  of  Physiology,"  1902,  vol.  viii,  p.  xxxii. 

^  Arteaga:  Ibid.,  1901,  vol.  vi,  p.  175. 

*  Lusk:   "Zeitschrift  fiir  Biologic,"  1901,  Bd.  xlii,  p.  43. 

^  Reilly,  Nolan,  and  Lusk:  "American  Journal  of  Physiology,"  1895,  vol.  i, 
p.  396. 

^  Reilly,  Nolan,  and  Lusk:   Loc.  cit. 

''  Stiles  and  Lusk:  "American  Journal  of  Physiology,"  1903,  vol.  x,  p.  67. 

^Mandel  and  Lusk:  "Deutsches  Archiv  fiir  klin.  Medizin,"  1904,  Bd. 
Ixxxi,  p.  479. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.    277 

in  human  diabetes  when  the  patient  is  given  a  diet  of  meat 
and  fat.     These  ratios  are  thus  comparable: 


ZINIZEE 

)   DOG.I 

Diabetes  Mellitus  in  Man.^ 

3.60 

3.60 

3-65 

3-(>5 

3.66 

3.66 

3.62 

A  remarkable  discovery  is  that  of  Falta,^  who  shows  that  a 
D  :  N  ratio  of  3.6  :  i  may  exist  in  dogs  after  removal  of  three 
of  the  parathyroids  and  the  pancreas. 

In  another  place  (p.  131)  it  has  been  shown  that  the  D  :  N 
ratio  does  not  vary  after  the  ingestion  of  sufficient  meat  to  double 
the  quantity  of  nitrogen  in  the  urine;  the  sugar  also  doubles. 
The  sugar  production  is  therefore  proportional  to  the  protein 
metabolism,  and,  apparently,  must  be  derived  from  protein. 

Various  objections  have  been  raised  to  this  statement. 
Other  experiments,  however,  confirm   the   above  proposition. 

Liithje*  gave  nutrose  to  a  depancreatized  dog.  Nutrose 
contains  casein  but  no  sugar.  The  dog  weighed  5.8  kilograms 
and  eliminated  11 76  grams  of  glucose  during  twenty-five  days. 
The  tissues  of  the  dog  could  not  possibly  have  contained  over 
232  grams  of  glycogen  at  the  beginning  of  the  experiment.  The 
source  of  the  sugar  could  not  have  been  the  animal's  store  of 
glycogen,  but  must  have  arisen  from  either  protein  or  fat. 

Pfiiiger^  would  have  it  that  fat  metabolism  is  the  principal 
source  of  sugar  in  diabetes. 

The  simplest  substance  from  which  sugar  may  be  constructed 
is  formaldehyde.  Long  ago,  Baeyer  suggested  that  the  formation 
of  sugar  in  the  leaf  was  through  a  condensation  of  formalde- 
hyde molecules  into  dextrose  and  Grubc^  has  shown  that  form- 

'  Stiles  and  Lusk:  Loc.  cit.,  p.  77.     (Details,  this  book,  p.  70.) 
^  Mandel  and  Lusk:   Loc.  cit.,  p.  479. 

'  Eppinger,  Falta,  and  Rudingcr:  "Zeitschrift  fiir  klinische  Medizin,"  1909, 
Bd.  Ixvii,  p.  392. 

*Luthje:  "Pfliiger's  Archiv,"  1904,  Bd.  cvi,  p.  160. 

'  Pflijger:   Ibid.,  1905,  Bd.  cviii,  p.  115. 

'  Grubc:  "Arch.  f.  d.  ges.  Physiol.,"  1908,  Bd.  cxxi,  p.  636. 


278  SCIENCE   OF  NUTRITION. 

aldehyde  perfused  through  the  liver  of  a  tortoise  is  converted 
into  glycogen. 

The  changes  described  are  according  to  the  following  for- 
mula: 

COH 


H— C— OH 

0 

OH— C— H 

■  11 

6    H— C— H 

H— C— OH 

H— C— OH 

Formaldehyde. 

CH2OH 
Dextrose. 

It  has  already  been  shown  that  protein  breaks  up  into  amino- 
acids  in  the  intestines,  and  that  such  amino-acids  when  ingested 
are  the  equivalent  in  metabolism  of  protein  itself  (p.  113). 
Are  such  amino-acids  convertible  into  dextrose? 

Knopf^  has  shown  that  asparagin  given  to  a  diabetic  dog 
yields  at  least  i  .3  grams  of  dextrose  for  each  gram  of  its  nitrogen 
metabolized.  Stiles  and  Lusk^  find  that  a  pancreatic  digest  of 
meat,  consisting  of  amino-acids,  when  given  to  a  phlorhizinized 
dog,  yields  2.4  grams  of  dextrose  for  each  gram  of  nitrogen. 
Embden  and  Salomon^  find  that  glycocoll,  alanin  and  asparagin 
increase  the  dextrose  output  in  a  diabetic  dog. 

Pfl tiger*  explains  that  the  amino-acids  stimulate  the  fat 
metabolism  in  the  liver  in  such  a  manner  as  to  insure  a  produc- 
tion of  dextrose  from  fat.  This  can  hardly  be  correct,  for  it 
would  be  a  most  remarkable  arrangement  if  amino-bodies  car- 
ried to  the  liver  of  a  starving  cat  under  the  influence  of  phlor- 
hizin,  and  the  same  quantity  carried  to  the  same  locality  in  a 
dog  with  pancreas  diabetes,  should  in  both  cases  stimulate 
exactly  the  same  sugar  production  from  fat. 

^  Knopf:   " Archiv  fiir  ex.  Path,  und  Pharm.,"  1903,  Bd.  xlix,  p.  123. 
^  Stiles  and  Lusk:   "American  Journal  of  Physiology,"  1903,  vol.  ix,  p.  380. 
^Embden  and  Salomon:    "Hofmeister's  Beitrage,"   1904,  Bd.  v,  p.  507; 
1904,  Bd.  vi,  p.  63. 

*  Pfliiger:  Loc.  cit.,  p.  187. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.    279 

The  true  situation  was  first  appreciated  by  Neuberg/  who 
found  glycogen  in  the  liver  and  lactic  acid  in  the  urine  of  a 
normal  rabbit  following  the  ingestion  of  alanin.  The  amino- 
acid  alanin  is  converted  into  lactic  acid  by  hydrolysis  with  elimi- 
nation of  ammonia.  The  ammonia  is  converted  into  urea. 
Arthur  Mandel  and  the  writer^  have  shown  that  d-lactic  acid 
is  completely  converted  into  dextrose  in  the  organism,  and  re- 
cently Ringer  and  the  writer^  have  given  20  gm.  of  i-alanin  to  a 
diabetic  dog  and  witnessed  its  complete  elimination  in  the  form 
of  urinary  sugar. 


CH3 

CHNH2  +  H,0- 

COOH 

Alanin. 


-> 


CH3 

CHOH  +  NH3 

COOH 

Lactic  acid. 


In  other  experiments  the  writer*  showed  the  probability  that 
glutamic  acid  was  convertible  into  sugar  in  so  far  as  it  could 
form  alanin  in  the  organism.  This  would  take  place  according 
to  the  following  reaction,  the  lactic  acid  being  converted  into 
dextrose : 


COOH 

1 

1 
CHj 

C  H2    " " 

+  H2O 

CH3 

CHNH2 

> 

CHOH  +  NH, 

COOH 

COOH 

Glutamic  acid. 

Lactic  acid. 

Or  it  may  be  that  the  cleavage  of  the  glutamic  acid  may  be 
brought  about  by  hydrolysis  of  the  (S-carbon  with  the  production 
of  glyceric  acid  as  follows: 

'  Neuberg  and  Langstein:  "Arch.  f.  Physiol.,"  1903,  Supplcmentband,p.  514. 
^  Mandel  and  L'usk:   "  Am.  Jour.  Physiol.,"  1906,  vol.  xvi,  p.  129. 

*  Unpublished. 

*  Lusk:   "Am.  Jour.  Physiol.,"  1908,  vol.  xxii,  p.  174. 


28o  SCIENCE  OP  ISrtJTEITION. 


COOH 

COOH 

CH2 

> 

CH3 

/?CH3 

+  2H2O 

CHJ  OH 

CHNH2 

CHOH 

COOH 

COOH 

Glutamic  acid. 

Glyceric  acid. 

The  glyceric  acid  would  then  be  converted   into   dextrose. 

A  substance  like  glycocoU  might  be  converted  into  glycollic 
acid,  and  this  reduced  to  glycolaldehyde,  a  body  whose  sub- 
cutaneous injection  leads  to  an  output  of  sugar  in  rabbit's 
urine.^    These  reactions  might  be  as  follows: 

CH2  HN2  COOH  +  H3O  =  CH2  OH  COOH  +  NH3 
GlycocoU.  Glycollic  acid. 

3CH3OHCOH      =         CgHiaOe 
Glycolaldehyde.  Dextrose. 

It  seems  probable  that  the  course  of  the  intermediary  meta- 
bolism involving  sugar  production  is  as  has  been  outlined  above, 
and  to  this  list  of  sugar-producers  may  be  added  aspartic  acid 
and  probably  serin. 

Giving  fat  with  meat  to  a  diabetic  will  not  ordinarily  in- 
crease the  sugar  in  the  urine.  The  writer  has  never  observed 
such  an  increase  in  any  of  the  work  of  his  laboratory.  A  large 
production  of  sugar  from  fat  has  been  elsewhere  reported^  and 
Cremer^  finds  that  glycerin  given  alone  will  increase  the  output 
of  sugar  in  the  urine. 

On  giving  meat  in  diabetes  the  fat  metabolism  is  reduced 
as  it  would  be  in  the  normal  organism,  and  yet  there  is  no 
effect  on  the  D  :  N  ratio,  and  therefore  the  latter  cannot  be 
influenced  by  the  quantity  of  fat  burned.  This  is  shown  in  a 
respiration  experiment  made  by  Mandel  and  Lusk*  on  a  dog 

^  Mayer:  "Zeitschrift  fur  physiologische  Chemie,"  1903,  Bd.  xxxviii,  p.  151. 
^Hartogh  and  Schumm:    "Archiv  fiir  ex.  Path,  und  Pharm.,"  1900,  Bd. 
xlv,  p.  II. 

^  Cremer:   "Miinchener  med.  Wochenschrift,"  1902,  Bd.  xxii,  p.  944. 

*■  Mandel  and  Lusk:  "American  Journal  of  Physiology,"  1903,  vol.  x,  p.  54. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.   281 

with  phlorhizin  glycosuria  whose  metabolism  starving  and  after 
meat  ingestion  was  as  follows: 

Calories  Calories  Calories, 

D:N.      FROM  Protein,   from  Fat.  Total. 

Fasting 3.69  80.2  274.4  354.6 

300  grams  meat 3.55  161.9  261.7  423.6 

The  protein  metabolism  doubled  when  meat  w^as  ingested, 
the  fat  metabolism  fell,  but  the  D  :  N  ratio  remained  constant. 

It  has  also  been  demonstrated  that  neither  exposure  to  cold 
nor  mechanical  exercise,  both  of  which  result  in  a  largely  in- 
creased metabolism  of  fat,  has  any  effect  on  the  sugar  output 
in  pancreas  diabetes,^  or  in  phlorhizin  glycosuria.^  Thus  the 
WTiter  found  in  a  phlorhizinized  dog  w^hich  had  been  rid  of 
glycogen  by  shivering  and  exercise,  that  the  composition  of  the 
urine  was  unchanged  as  the  result  of  travelling  1 500  meters  in  a 
revolving  wheel,  an  effort  which  would  have  more  than  doubled 
the  metabolism  of  fat  during  the  hour  when  the  exercise  was 
taken.  The  analytical  data  for  two-hour  periods  were  the 
following : 

Dextrose.    Nitrogen.         D:N. 

Rest 4-57  1-26  3-63 

Work,  1500  meters  during  ist  hour 4.62  1.26  3.67 

In  this  experiment  exercise  was  without  influence  on  the 
excretion  of  nitrogen.  If,  however,  the  animal  contains  residues 
of  glycogen  which  as  a  result  of  exercise  are  converted  into  sugar 
and  eliminated,  then  there  is  also  an  increased  nitrogen  elimina- 
tion as  the  result  of  work.  This  is  suggestive  of  a  chemical 
union  between  glycogen  and  nitrogenous  substances  which 
may  be  similar  in  nature  to  that  of  the  hypothetical  amino-sugars 
of  Liithje  and  of  Murlin  (see  p.  123). 

If  a  production  of  dextrose  from  fat  metabolism  be  possible, 
it  must  be  due  to  a  qualitative  alteration  in  the  metabolism  in 

'  Allard:  " Archiv  fur  exper.  Path,  und  Pharm.,"  1908,  Bd.  lix,  p.  iii;  Seo, 
Ibid.,  p.  341. 

*Lusk:   "American  Journal  of  Physiology,"  1908,  vol.  xxii,  p.  163. 


282  SCIENCE   OF   NUTRITION. 

rare  and  special  cases.  A  high  authority,  von  Noorden/  writes: 
"In  all  probability  we  may  even  now  make  the  statement  that 
there  are  a  few  cases  of  diabetes  in  which  more  sugar  is  ex- 
creted than  can  be  accounted  for  by  the  amount  of  carbohydrate 
available,  and  the  maximum  quantity  of  protein  that  could 
have  been  disintegrated,  and  that  in  these  cases  fat  must  be 
looked  upon  as  the  source  of  the  excess." 

The  theory  of  the  origin  of  sugar  from  fat  is  supported  by 
Falta,^  who  finds  a  largely  increased  sugar  output  after  adminis- 
tering adrenalin  to  dogs  with  pancreas  diabetes.  Among  the 
cases  of  high  D  :  N  ratios  in  human  diabetes  reported  from  von 
Noorden's  clinic  that  described  by  Bernstein,  Bolaffio  and 
Westenrijk^  is  the  most  remarkable.  The  ratio,  after  deducting  the 
carbohydrates  ingested  in  the  food,  often  reached  D  :  N: :  10  :  i. 
The  ammonia  nitrogen  ran  as  high  as  86%  of  the  total  nitrogen, 
/?-oxybutyric  acid  reached  sixty  grams  per  day,  and  nitrogen 
equilibrium  was  maintained  on  a  diet  containing  only  10.6 
grams  of  nitrogen.  Such  figures  reveal  a  most  exceptional  type 
of  diabetes  mellitus.  The  high  ratios  in  diabetes  are  explained 
by  Falta  as  being  due  to  very  great  activity  on  the  part  of  the 
adrenals  which  not  only  inhibits  the  internal  secretion  of  the 
pancreas,  but  also  causes  a  production  of  sugar  from  fat.  How- 
ever, Ringer,  working  in  the  author's  laboratory,  finds  that  if 
adrenalin  be  administered  to  a  fasting  phlorhizinized  dog, 
although  the  first  administration  of  the  drug  may  bring  about 
an  elimination  of  "extra  sugar"  which  may  be  discharged  from 
the  glycogen  repositories  of  the  body  on  account  of  the  anemia 
of  the  tissues  (see  p.  255),  a  second  injection  of  adrenalin  may  be 
entirely  without  influence  on  either  the  sugar  or  nitrogen  elimina- 
tion. This  indicates  that  adrenalin  does  not  cause  a  production 
of  sugar  from  fat. 

^  Von  Noorden:   "Diabetes,"  Herter  Lectures,  1905,  p.  80. 
^  Eppinger,    Falta   and    Rudinger:     "Zeitschrift   ftir   klinische    Medizin," 
1908,  Bd.  Ixvi,  p.  I. 

^  Bernstein,  Bolaffio,  and  Westenrijk:  "Zeitschrift  fiir  klinische  Medizin," 
1908,  Bd.  Ixvi,  p.  I. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.    283 

Falta  explains  the  results  of  many  experiments  by  stating 
that  while  the  secretory  activities  of  both  thyroid  and  adrenals 
are  each  stimulated  by  the  secretions  of  the  other,  the  activity 
of  the  pancreas  is  in  like  manner  inhibited  by  the  secretions  of 
the  other  two  glands.  Therefore  supersecretion  of  adrenalin 
inhibits  the  secretory  function  of  the  pancreas  so  that  the  organ- 
ism can  no  longer  oxidize  carbohydrates  and  at  the  same  time 
it  stimulates  the  thyroid,  causing  increased  protein  metabolism. 
Furthermore  in  exophthalmic  goiter,  where  there  is  super- 
secretion  in  the  thyroid  gland,  there  is  a  tendency  to  glycosuria, 
and  it  is  believed  that  true  diabetes  has  been  induced  by  this 
cause. ^  Administration  of  thyroid  extracts  to  dogs  also  produces 
glycosuria.  Cecil,^  working  under  Opie's  direction,  finds  lesions 
of  the  pancreas  in  cases  of  diabetes  associated  with  exophthalmic 
goiter.  It  has  already  been  noted  that  the  extirpation  of  the 
parathyroids  in  depancreatized  dogs  raises  the  urinary  D  :  N 
ratio  from  2.8  to  3.65,  which  shows  that  these  glands  are  in  some 
way  related  in  their  influence  over  carbohydrate  metabolism. 

A  question  of  special  interest  is  the  cause  of  the  two  D  :  N 
ratios,  2.8  :  i  and  3.65  :  i.  The  former  represents  a  production 
of  45  per  cent.,  the  latter  one  of  58  per  cent,  of  sugar  from  meat 
protein.  In  neither  case  can  ingested  dextrose  be  burned. 
It  is,  of  course,  possible  that  the  sugar  production  varies  under 
different  circumstances;  that  is  to  say,  the  organism  (liver  ?)  may 
be  able  at  times  to  produce  sugar  from  a  certain  class  of  protein 
decomposition  products,  and  at  other  times  not.  For  example, 
it  has  been  noted  (p.  279)  that  glutamic  acid  is  convertible  into 
dextrose  in  the  dog,  but  Neuberg^  testifies  that  it  may  also  be 
converted  into  butyric  acid  from  which  sugar  cannot  be  formed. 
Or,  one  may  adopt  the  hypothesis  of  Mandel  and  Lusk,^  which 

'Magnus-Levy:  von  Noorden's  "  Ilandbuch  des  Stoffwechsels,"  1907, 
Bd.  ii,  p.  333. 

^  Cecil :  "Journal  of  Experimental  Medicine,"  1909,  vol.  xi,  p.  266. 

'  Brasch  and  Ncuberg:    "  Biochemische  Zeitschrift,"  1908,  Bd.  xiii,  p.  299. 

*  Mandel  and  Lusk:  "Deutsches  Archiv  fiir  klinische  Medizin,"  1904,  Bd. 
Ixxxi,  p.  491. 


284  SCIENCE   OF  NUTRITION. 

assumes  a  difference  between  a-colloid  dextrose  and  /?-colloid 
dextrose  existing  in  the  blood.  By  a-dextrose  is  understood  the 
amount  of  dextrose  represented  by  the  ratio  D  :  N  :  :  2.8  :  i, 
or  45  per  cent,  of  the  protein.  The  /?-dextrose  represents  the 
additional  13.6  per  cent,  of  the  protein,  when  the  ratio  3.65  :  i 
is  present.  The  ratio  would  depend  on  the  combustion  or  non- 
combustion  of  the  /?-dextrose.  If  the  latter  burns,  it  must  do  so 
as  a  complex,  for  as  free  dextrose  it  would  be  eliminated  in  the 
urine. 

This  theory  of  a  difference  in  chemical  union  would  explain 
the  fact  discovered  by  Straub^  for  carbon  monoxid  "diabetes" 
and  by  Seelig^  for  glycosuria  following  ether  inhalation,  that 
sugar  appears  in  the  urine  in  large  quantity  if  a  dog  be  fed 
with  meat,  but  disappears  if  the  animal  be  given  carbohydrate 
alone.  Seelig  found  no  glycosuria  when  an  intravenous  in- 
fusion of  oxygen  was  administered  at  the  same  time  that  ether 
was  given.  It  may  be  that  lack  of  oxygen  causes  a  dissociation 
of  either  a-  or  ^-colloid  dextrose  derived  from  protein,  which 
dextrose  then  appears  in  the  urine.  This  suggestion  is,  how- 
ever, highly  speculative. 

One  of  the  very  pronounced  characteristics  of  the  diabetic 
is  his  constant  emaciation.  There  is  usually  a  larger  excretion 
of  nitrogen  in  the  urine  than  is  necessary  for  a  healthy  person. 
It  may  be  recalled  that  carbohydrates  diminish  the  protein 
metabolism,  and  also  that  a  person  may  support  life  on  meat  and 
fat  alone  without  tissue  waste.  But  in  this  latter  case  there  is 
a  supply  of  carbohydrate  derived  from  protein  metabolism. 
This  is  also  true  in  starvation.  But  when  the  protein  sugar  is 
withdrawn  from  the  tissue  cells  in  diabetes,  there  is  at  once  a 
largely  increased  protein  metabolism.  This  is  most  obvious  in 
fasting  animals  treated  with  phlorhizin,  as  this  glycosuria  can 
be  immediately  induced.  The  increase  in  protein  metabolism 
is  most  marked  where  the  higher  D  :  N  ratio  exists.     In  this 

'  Straub:   "  Archiv  fiir  ex.  Path,  und  Pharm.,"  1896,  Bd.  xxxviii,  p.  139. 
^  Seelig:  Ibid.,  1905,  Bd.  Hi,  p.  481. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.    285 

connection  the  following  experiments  on  fasting  animals  are 
suggestive : 

TABLE    ILLUSTRATING    THE    INFLUENCE    OF    DIABETES    ON 
PROTEIN  METABOLISM. 


GOAT.I 

D0G.2 

D. 

N. 

D:N. 

D. 

N. 

D:N. 

Fasting 

20.33 
26.08 
23-39 

19.01 

372 
3-71 
4.90 
8.83 
8.06 
6.84 

4-15 
2-95 
2.90 
2.78 

63-55 
65-30 
65.84 
64.60 

4-04 

4.17 

12.66 

18.76 

i8.S7 
17.29 

Fasting 

Fasting  and  diabetic 

5.02 
3.38 
3-54 
3-74 

In  the  goat  the  protein  metabolism  rose  to  238,  in  the  dog  to 
450  per  cent,  of  that  in  the  normal  animals,  as  the  result  of  the 
loss  of  the  influence  of  the  small  quantity  of  protein  sugar 
produced  in  starvation. 

Falta,  Grote,and  Staehehn^  found  a  rise  in  the  protein  metab- 
olism of  fasting  dogs  which  had  been  depancreatised,  equal  to 
five-fold  the  normal  amount. 

In  the  case  of  diabetes  mellitus  reported  by  Mandel  and 
Lusk  where  the  ratio  D  :  N  was  3.65  :  i,  it  was  found  that  the 
ingestion  of  broths  containing  7.7  grams  of  nitrogen  was  fol- 
lowed by  an  elimination  of  21.7  grams  of  nitrogen  in  the  urine 
or  a  loss  of  body  nitrogen  approximating  14  grams.  The  patient 
was  greatly  emaciated,  and  passed  this  day  in  bed.  He  could 
not  be  maintained  in  nitrogen  equilibrium  with  19  grams  of 
protein  nitrogen  in  the  food,  but  was  in  nitrogen  equilibrium 
when  given  27  grams.  In  all  cases  of  intense  diabetes  this  fac- 
tor of  an  increased  protein  metabolism  must  be  considered. 
In  mild  cases  in  which  sugar  disappears  from  the  urine  when 

*  Lusk:   "Zeitschrift  fur  Biologic,"  1901,  Bd.  xlii,  p.  43. 

*  Reilly,  Nolan,  and  Lusk:  "American  Journal  of  Physiology,"  1895,  vol.  i, 

P-  397- 

»  Falta,  Grote,  and  Staehelin:  "Hofmeister's  Beitrage,"  1907,  Bd.  x,  p.  199. 


286  SCIENCE   OE  NUTRITION. 

carbohydrates  are  cut  out  of  the  food,  and  in  which  the  patient 
may  burn  his  protein  sugar,  the  protein  metabohsm  is  not 
different  from  that  of  a  normal  person  Hving  on  meat  and 
fat. 

Among  the  earhest  investigations  of  Pettenkofer  and  Voit^  was 
a  respiration  experiment  on  a  diabetic  individual.  The  authors 
compared  the  metabolism  of  a  diabetic  with  that  of  a  normal 
man,  as  is  indicated  in  the  following  table: 

COMPARISON   OF   A   NORMAL   AND   A  DIABETIC   MAN. 

Grams  Grams  Burned 

IN  THE  Food.  in  the  Body. 

Healthy  man,  Protein 120  120 

"           "      Fat 112  83 

_"     _      "      Sugar 344  344 

Diabetic  man,  Protein 107  158 

"      Fat 108  158 

"     Sugar 337  o 

(337  grams  of  sugar  in  the  urine.) 

It  is  seen  here  that  the  fat  and  protein  metabolism  are  in- 
creased in  order  to  compensate  for  the  non-combustion  of  the 
sugar.  Several  years  later,  on  the  basis  of  these  experiments, 
E.  Voit  calculated  that  a  diabetic  on  a  moderate  mixed  diet 
yielded  1015  calories  per  square  meter  of  surface,  while  the 
normal  individual  of  similar  build  produced  1020  calories. 
Falta,^  working  with  Benedict  in  Boston,  finds  that  the  total 
metabolism  of  men  suffering  from  severe  diabetes  is  unchanged 
from  the  normal. 

The  diabetic  condition,  therefore,  does  not  involve  a  decrease 
in  the  quantity  of  energy  produced,  but  only  an  alteration  in  the 
source  of  the  energy.  This  fact  can  be  made  still  more  strik- 
ingly apparent  by  comparing  the  metabolism  of  a  normal  fasting 
dog  with  the  metabolism  of  the  same  dog  made  diabetic  with 
phlorhizin.  Such  an  experiment  was  first  done  by  the  writer^  on 
a  fasting  dog  of  11  kilograms  and  with  the  following  results: 

'  Pettenkofer  and  Voit:  "Zeitschrift  fur  Biologie,"  1867,  Bd.  iii,  p.  380. 
^Falta:  "Wiener  klin.  Wochenscher.,"    1909,  Bd.  xxii,  No.  16. 
^  Lusk:  "Zeitschrift  fiir  Biologie,"  1901,  Bd.  xlii,  p.  31. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.    287 

COMPARISON    OF   NORMAL   AND    DIABETIC   METABOLISM   IN 
THE  SAME  FASTING  DOG. 

Grams  Burned  Calories  from 

m  THE  Body.  Metabolism. 

Normal,  Protein 20.19  80.68 

Fat 55.87  526.13 

Total 606.81 

Diabetic,  Protein 67.38  128.08 

Fat 51.15  481.69 

Total 605.77 

(39.4  grams  dextrose  in  urine.     D  :  N  ::  3.65  :  i) 

It  is  apparent  from  the  above  experiment  that  the  protein 
metabohsm  of  the  diabetic  dog  increased  to  333  per  cent,  of  that 
of  the  dog  when  normal.  The  fat  metabohsm  shghtly  decreased, 
but  the  total  energy  derived  from  the  metabolism  was  exactly 
the  same  in  both  cases. 

Rubner^  has  rightly  criticized  this  experiment  for  neglect  to 
record  the  temperature  at  which  it  was  carried  out.  Rubner 
has  repeated  the  work  when  the  dog  was  kept  in  a  room  having 
the  temperature  of  33°,  but  the  D  :  N  ratio  in  this  dog  was  only 
2.8  :  I  on  the  second  day  of  diabetes,  and  Rubner  also  did  not 
take  into  account  the  preliminary  clearing  out  of  the  body 
sugar  which  raised  his  ratio  on  the  first  day.  These  facts,  how- 
ever, do  not  invalidate  his  conclusions. 

Rubner  finds  the  metabolism  on  the  fasting  days  to  be  the 
equivalent  of  477.8  calories  and  on  the  diabetic  days  to  be  510.4, 
an  increase  of  32.3  calories  per  day  in  diabetes.  This  increase 
Rubner  attributes  to  the  specific  dynamic  action  of  the  increased 
protein  metabolism.  This  increase  in  protein  destruction  in  the 
diabetic  dog  amounted  to  the  equivalent  of  loi.i  calories. 
Rubner  therefore  calculates  that  through  the  extra  metabolism 
of  the  equivalent  of  100  calories  in  protein,  31.9  of  extra  heat 
production  arises.  This  agrees  with  his  values  elsewhere  dis- 
cussed (p.  160).  Rubner's  results  do  not  conflict  with  the 
writer's  experiment,  for  at  a  room  temperature  below  ^2i°  the 

*  Rubner:  "Gesetze  des  Energieverbrauchs,"  1902,  p.  370. 


288  SCIENCE   or  NUTRITION. 

calories  of  the  chemical  regulation  of  temperature  are  replaceable 
by  those  derived  from  the  specific  dynamic  action  of  protein, 
without  any  alteration  in  the  total  of  the  metabolism. 

The  specific  dynamic  action  of  protein  ingested  in  diabetes 
is  also  illustrated  in  the  experiment  given  on  page  281.  The 
knowledge  at  hand  makes  it  possible  to  estimate  the  energy 
value  of  protein  to  the  diabetic.  It  may  be  calculated  from  the 
D  :  N  :  :  3.65  :  i  that  52.5  per  cent,  of  the  energy  in  meat  pro- 
tein is  lost  to  the  organism  in  the  form  of  dextrose.  Rubner 
teaches  that  28.5  per  cent,  of  the  energy  of  meat  protein  is  never 
utilized  in  the  service  of  the  life  processes  of  the  cell,  but  is 
liberated  as  free  heat  (p.  163).  There  remains  a  balance  of  only 
19  per  cent,  which  is  actually  available  for  maintenance  of  the 
vital  activities  in  diabetes.  The  three-  to  five-fold  increase  in 
protein  metabolism,  however,  nearly  neutralizes  this  great  waste 
of  energy,  and  leaves  the  fat  metabolism  very  much  as  in  the 
normal  organism. 

The  distribution  of  the  energy  from  protein  in  the  diabetic, 
as  described  above,  may  thus  be  summarized : 

100  Protein  Calories. 
28.5  for  cleavage  and  deamination.     71.5  for  life  processes. 
Deduct 52.5  energy  in  dextrose. 

19.0    balance  available  =  x. 

The  production  of  dextrose  from  protein  involves  the  ab- 
sorption of  a  good  quantity  of  oxygen.  Magnus-Levy,^  calcu- 
lating that  60  grams  of  dextrose  arise  from  those  decomposition 
products  of  100  grams  of  protein  which  do  not  appear  in  the 
urine  and  feces  (p.  37),  gives  the  following  table  indicating  the 
requirement  for  oxygen  when  protein  burns  in  diabetes : 

100  grams  protein =   38.6  C.  4.24  H.  9.24  O. 

60     "        dextrose =   24.0  C.  4.0    H.  32.0    O. 


Balance   requiring      re- 
spiratory O ■\-   14.6  C.  -f-  0.24  H.  — 22.8    O. 

*  Magnus-Levy:  "Archiv  fiir  Physiologic,"  1904,  p.  379.  ' 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.    289 

A  further  calculation  showed  that  the  respiratory  quotient 
for  protein  in  this  diabetic  condition  was  reduced  from  the  nor- 
mal of  0.808  to  0.613.  Oxygen  is  not  only  used  to  form  water 
and  carbon  dioxid,  but  it  is  also  used  to  form  sugar,  jjence 
in  severe  diabetes  the  respiratory  quotient  may  fall  below  that 
representing  fat  metabolism. 

The  preeminence  of  fat  metabolism  in  the  diabetic  as  the 
mainstay  of  his  organism  leads  to  inquiry  as  to  the  origin  of 
the  fatty  acid  called  /?-oxybutyric  acid,  and  of  aceto-acetic  acid 
and  acetone  which  are  directly  derived  from  it.^  Whence  do 
these  acetone  bodies  arise?  They  wTre  at  first  supposed  to 
come  from  dextrose,  following  a  chemical  process  analogous 
to  the  butyric  acid  fermentation  of  carbohydrates,  but  it  was 
soon  discovered  that  in  normal  persons  the  acetone  bodies  were 
especially  found  in  the  fasting  state.  IMany  then  attributed 
the  presence  of  acetone  to  the  specific  breakdown  of  body 
protein,  since,  when  protein  was  given  in  the  food,  the  acetone 
bodies  disappeared  in  the  urine.  However,  Magnus-Levy^  has 
reported  a  case  of  a  boy  in  coma  who  eliminated  an.  average  of 
97.5  grams  of  /?-oxybutyric  acid  and  aceto-acetic  acid  daily 
for  three  days  in  addition  to  an  unmeasured  quantity  of  acetone 
in  the  breath,  and  during  this  time  the  protein  metabolism 
amounted  to  90  grams,  of  which  latter  at  least  40  grams  appeared 
as  sugar  in  the  urine.  The  97.5  grams  of  acetone  bodies  in 
this  case  could  not  have  been  entirely  derived  from  the  90  grams 
of  protein,  but  they  must  have  originated  largely  from  fat. 

Stadelman'  first  pointed  out  the  relationship  between  the 
formation  of  /3-oxybutyric  acid  and  the  occurrence  of  coma. 
Coma  has  been  compared  to  the  sword  of  Damocles  which 
hangs  suspended  over  every  diabetic.  It  has  been  discovered 
that  whenever  the  organism  is  thrown  suddenly  from  a  carbo- 
hydrate regimen  to  a  combustion  of  fat  the  acetone  bodies  appear 

'This  description  is  taken  from  Lusk:    Metabolism  in  Diabetes,  Harvey 
Society  Lecture,  "Archives  of  Internal  Medicine,"  1909,  vol.  iii,  p.  i. 
*  Magnus- Levy:   "Ergebnisse  d.  inn.  Med.,"  1908,  Bd.  i,  p.  374. 
'Stadelman:  "  Experimcntelle-klinische  Untersuchungen,"  Stuttgart,  1890. 
19 


290 


SCIENCE   OF  NUTRITION. 


in  the  urine.     This  condition  is  greatly  intensified  in  diabetes 
when  even  the  sugar  derived  from  protein  is  not  burned. 

Knoop/  through  cleverly  devised  experiments,  has  shown 
that  the  oxidation  of  fatty  acids  in  the  body  is  effected  by  an 
attack  on  the  fatty  molecule  at  the  carbon  in  the  ^-position. 
Thus,  the  first  step  in  the  metabolism  of  butyric  acid  would  be 
the  oxidation  of  its  /3-carbon  atom  as  follows : 


CH3 

CH3 

^-CH  2 

> 

CHOH 

1 

a-CH2 

0 

1 
CH2 

COOH 

COOH 

Butyric  acid. 

13- 

■oxybutyric  acid. 

In  a  similar  manner,  caproic  acid  would  first  be  oxidized  at 
its  beta-carbon  atom  and  then  on  further  oxidation  would  lose 
two  atoms  of  carbon  and  be  converted  into  butyric  acid,  which, 
in  turn,  becomes  /?-oxybutyric  acid.  These  reactions  may  be 
written  as  follows : 


CH3 

CH3 

CH3 

CH3 

I 

CH2 

CH2 

CH,      

1    " 

-> 

CH2 

1 

CH2 

1 
CH2 

1 
CH2 

1 
CH2 

CH2  +  0 

CHOH  +  0 

CO  +  4O 

COOH 

CH2   — - 

-> 

CH2     — 

-> 

CH2 

1 

H26       ' 

COOH 

COOH 

COOH 

2CO2 

Caproic  acid, 

Such,  indeed,  is  believed  to  be  the  method  of  successive 
oxidation  of  ah  the  fatty  acids,  of  palmitic  acid,  C^oH^fi^,  and 
of  stearic  acid,  C^Ji^^O^.  It  is  evident  that  each  successive 
oxidation  carries  away  two  carbon  atoms  and  that  /?-oxybutyric 
acid  can  be  produced  only  from  fatty  acids  having  an  even 
number  of  carbon  atoms.     Valerianic  acid,  for  example,  with 

^  Knoop:   "  Beitr.  z.  chem.  Physiol,  u.  Path.,"  1904,  Bd.  vi,  p.  150. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.    29I 

five  atoms  of  carbon,  can  not  yield  /3-oxybutyric  acid.  The 
organism  has  an  apparent  preference  for  fats  with  an  even 
number  of  carbon  atoms,  and  each  of  these  fatty  acids  on  its 
way  in  metabolism  yields  a  molecule  of  /3-oxybut}Tic  acid. 

Each  molecule  of  butyric  acid  can  yield  one  of  ^-oxybutyric 
acid.  It  has  been  calculated  by  Magnus-Lev}^^  that  loo  grams 
of  neutral  fat  made  of  stearin,  palmitin,  and  olein  may  yield 
36.2  grams  of  ^-oxybut}Tic  acid.  It  is,  therefore,  evident  that 
the  higher  fatty  acids  are  the  more  valuable  nutriment.  Butter, 
with  its  high  content  of  butyric  acid,  largely  increases  the  output 
of  the  acetone  bodies  in  diabetes.  Fifty  to  100  grams  of  butter 
fat  when  administered  to  a  diabetic  may  raise  his  acetone  output 
four  to  eightfold.^     Oleomargarin  is  to  be  preferred. 

Joslin^  has  sho\Mi  that  oleic  acid  yields  acetone  more  readily 
in  diabetes  than  do  palmitic  and  stearic  acids. 

Normal  oleic  acid  has  a  double  band  between  the  two  carbon 
atoms  which  are  in  the  middle  of  its  chain;  in  other  words  it  is 
an  unsaturated  fatty  acid.  Such  acids  on  oxidation  break  up 
into  two,  the  cleavage  taking  place  at  the  double  link.  In  the 
case  of  oleic  acid  the  following  reactions  take  place : 

CgHi^CH  :  CHCjHi^COOH     > 

Oleic  acid. 

CgH„COOH  +  COOH  C,H„COOH 

Pelargonic  acid.  Azelaic  acid. 

Leathes^  has  pointed  out  that  the  oleic  acid  found  in  the 
liver  does  not  yield  these  acids,  but  only  caproic  acid  is  found 
on  oxidation.  Leathes  therefore  states  that  the  liver  acts  on 
the  double  linkage  causing  its  transposition  on  the  fatty  acid 
chain  to  a  point  where  the  oxidation  becomes  more  easy. 
Furthermore  Leathes  finds  that  the  liver  causes  the  formation 
of  new  double  bands  in  fatty  acids  which  reach  it,  thereby 
preparing  them   for   readier   oxidation.     The   liver   therefore 

'  Magnus-Levy:   "Ergebnisse  d.  inn.  Med.,"  1908,  Bd.  i,  p.  384. 
^  Fcjcs:   "Magyar  orvosi  Archivum,"  1907,  Bd.  viii,  p.  335. 

*  Joslin:   "Jour.  Med.  Research,"  1904,  Bd.  xii,  p.  433. 

*  Leathes:    Harvey  Society  Lecture,  "Lancet,"  1909,  vol.  clxxvi,  p.  593. 


292  SCIENCE   OF  NUTRITION. 

desaturates  fatty  acids  and  transposes  unsaturated  linkages, 
in  the  interest  of  the  readier  oxidation  of  the  fats  when  they 
are  returned  to  the  tissues  to  yield  energy  for  the  maintenance 
of  life.  This  explains  the  filling  of  the  liver  with  fat  when  the 
organism  no  longer  burns  carbohydrates.  The  fat  of  the  sub- 
cutaneous layers  is  transported  to  the  liver  to  be  worked  over 
and  is  then  distributed  to  the  cells  of  the  organism  in  a  form 
which  is  more  readily  available  than  before. 

One  can  realize  from  this  that  the  short  chains  of  oxy-acids 
derived  from  protein  in  metabolism  are  much  more  available 
for  cellular  metabolism  than  are  the  ordinary  fatty  acids,  and 
would  be  oxidized  first. 

The  story  of  the  formation  of  /?-oxybutyric  acid  does  not 
end  with  the  metabolism  of  fat,  for  many  of  the  amino-acids 
of  protein  yield  this  acid  in  metabolism.  From  the  experiments 
of  Embden,  Salomon  and  Schmidt,^  Baer  and  Blum,^  it  has  been 
discovered  that  leucin  may  yield  /?-oxybutyric  acid,  whereas 
amino-butyric  and  normal  amino-caproic  acids  do  not.  Fried- 
rich  Miiller,  in  his  Herter  lectures,  mentioned  the  fact  that  he 
had  administered  amino-valerianic  acid  to  a  diabetic  patient, 
with  resulting  increase  in  the  /?-oxybutyric  acid  excretion. 

These  statements  are  all  conformant  with  the  idea  of  a 
^-oxidation  of  fatty  molecules.  Thus,  when  a-amino- valerianic 
acid  is  ingested,  it  undergoes  hydrolysis  in  the  intestinal  wall 
and  loses  ammonia.  Its  further  oxidation  results  in  the  produc- 
tion of  butyric  acid,  which  is  now  oxidized  at  the  /?-carbon. 
The  reaction  is  as  follows: 

(-.H  o  CH  ,  CH  ™ 

I  I  I 

CH2  CH2  CH, 

I  I  I 

CHj  +  H2O  CH2  4-  2O  CH, 

I  I  I 

CHNH,        CHOH        COOH 


COOH  >  COOH  >  CO^  +  U.O 

a-Aminovalerianic  acid.  Butyric  acid. 

^  Embden,  Salomon  and  Schmidt:  "  Beitr.  z.  chem.  Physiol,  u.  Path.,"  1906, 
Bd.  viii,  p.  129. 

^  Baer  and  Blum:  "Arch.  f.  exper.  Path.  u.  Pharmakol.,"  1906,  Bd.  Iv,  p.  89. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.    293 


In  a  similar  manner  amino-butyric  acid  and  amino-caproic  acid 
would  produce,  respectively,  propionic  and  valerianic  acids, 
neither  of  which  is  convertible  into  ^-oxybutyric. 


CH3  CH3 

CH3      >      CH,     > 

CHNH2  +  H2O     CHOH  +  2O 


COOH 

Amino-butyric  acid. 


COOH 

-oxybutyric  acid. 


CH, 

I 
CH, 

I 
COOH 

H26  +  CO2 

Propionic  acid. 


In  the  case  of  leucin,  iso-valerianic  acid  would  be  the  inter- 
mediary product,  and  it  has  been  shown  that  this  fatty  acid 
with  its  broken  chain  is  convertible  into  /?-oxybutyric  acid  in 
the  organism. 


CH3  CH3 

CH 

I 
CH, 


-> 


CH3  CH3 
\/ 
CH 

I 
CH2 

I 
CHOH 


-> 


CH3  :CH3 
\    — 

/9CH 

CH3 
CHOH 

CH,      > 

CHj 

COOH 

COOH 

co'z+h/o 

Isovalerianic   j 
acid. 

j3-oxybutyric 
acid. 

CHNH2  +  H,0 

COOH  COOH 

Leucin.  a-oxyisobutyl 

acetic  acid. 

It  may  also  be  added  that  Embden^  has  shown  that  homo- 
gentisic  acid  and  its  precursors  tyrosin  and  phenylalanin  yield 
acetone  on  perfusion  through  an  excised  liver.  Hence  the 
benzol  ring  when  it  is  broken  in  the  body  yields  a  normal  product 
of  fatty  acid  oxidation  (see  p.  136). 

Ketonic  acids  are  also  intermediary  products  here,  resulting 
from  the  oxidation  of  the  oxy-acids.  Neubauer^  gives  the 
following  general  scheme  for  the  oxidation  of  amino-acids: 


R 


Deamination 


R 


R 


Oxidation 
I  I  and  I 

CHNH2        and  oxidation         CO        CO,  cleavage      COOH 

COOH     ■         >  COOH        > 

'  Embden,  Salomon,  and  Schmidt:  Loc.  cit. 

^Neubauer:  "DcutschcsArchivfurklinischeMedizin,"  iQOQ.Bd.xcv,  p.  211. 


294  SCIENCE   OP  NUTRITION. 

Dakin^  has  shown  that  peroxid  of  hydrogen  acting  on  amino- 
acids  converts  them  into  ketonic  acids.  After  a  similar  fashion 
acetone  arises  from  ^-oxybutyric  acid,  as  follows: 


CH3 

CH3 

CH3 

CHOH 

1 

+  0 

1 

CO 

1 
CO 

1 

1 
CH2 

1 

> 

CH2      — 

-> 

CH3 

COOH 

COOH 

C02 

i-oxybutyric  acid. 

Aceto-acetic  acid. 

Acetone. 

Since  acetone  is  with  difficulty  oxidized  in  the  body,  it  is 
probable  that  in  the  normal  process  of  oxidation  the  acetoacetic 
acid  formed  is  directly  converted  into  two  molecules  of  acetic 
acid,  and  these  through  formic  acid  into  carbon  dioxid  and  water, 
as  follows: 

CH3  CH3  CO2  +  HjO 

I  I  > 

CO     +  H2O      COOH  HCOOH  ->   COj  +  H2O 

CH2     >      CH3  CO,  +  H2O 

I  1  ^> 

COOH  COOH  HCOOH  >   COj  +  H^O 

Acetoacetic  Acetic  Formic 

add.  acid.  acid. 

Amino-acids  which  form  sugar  on  ingestion,  such  as  glyco- 
coU,  alanin,  aspartic  acid  and  glutamic  acid,  do  not  form 
/?-oxybutyric  acid,  but  may  rather  decrease  the  quantity  pro- 
duced, especially  if  the  sugar  formed  can  burn.  This  ex- 
plains why  the  acidosis  in  fasting  is  reduced  on  ingestion  of  meat. 
Baer  and  Blum^  gave  10  grams  of  alanin  to  a  dog  which  received 
about  a  gram  of  phlorhizin  daily.  The  sugar  output  was  raised 
from  19.5  to  21.5  grams.  Since  we  have  seen  that  alanin  is 
completely  convertible  into  dextrose,  it  follows  that  much  of  it 
must  have  been  burned  in  the  incompletely  phlorhizinized  dog. 
Therefore,  the  acetone  excretion  decreased  and  /?-oxybutyric 
acid  disappeared.     The  profound  effect  of   the  ingestion  of 

^  Dakin:  "Journal  of  Biological  Chemistry,"  1908,  vol.  iv,  p.  221. 

^  Baer  and  Blum:    "  Beitr.  z.  chem.  Physiol,  u.  Path.,"  1907,  Bd.  x,  p.  90. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING,    295 

glutaric  acid  in  reducing  sugar  and  nitrogen  output  as  well  as 
the  acetone  bodies  may  find  a  similar  explanation.  It  is  certain 
that  the  skilfully  planned  work  of  Baer  and  Blum  loses  a  large 
part  of  its  significance  because  of  the  too  small  and  too  infre- 
quent dosage  with  phlorhizin. 

Magnus-Levy^  gave  11.7  grams  of  ^fl-oxybutyric  acid  to  a 
normal  dog.  This  was  completely  burned.  He  then  gave 
1 1.5  grams  to  a  phlorhizinized  dog,  with  the  result  that  there  was 
an  increased  elimination  of  7.6  grams  of  /?-oxybutyric  acid  and 
acetone.  Since  some  acetone  was  eliminated  in  the  breath,  it 
is  evident  that  the  animal  had  largely  lost  the  power  to  burn 
ingested  /?-oxybutyric  acid. 

On  the  basis  of  work  on  a  diabetic  and  comatose  boy  weigh- 
ing 32  kg.,  Magnus-Levy^  makes  the  following  computation  of 
metabolism.  He  purposely  assumes  a  high  requirement  of 
energy  for  a  lad  of  this  size,  or  50  to  55  calories  per  kilogram, 
which  calls  for  a  total  of  1600  to  1700  calories.  The  boy 
burned  90  grams  of  protein  and  perhaps  200  grams  of  fat: 

Calories. 
90  grams  protein  =      369  calories  \  =2278 

200  grams  fat  =  i  ,909  calories  /   ' 

Deduct  97.5  grams  oxybutyric  acid,  443  calories  1 

I-  =      628 

Deduct  50  grams  urinary  sugar,  185  calories  ..   J 

Calories  available 1650 

Here  we  perceive  an  extreme  case  of  diabetic  metabolism 
in  which  half  the  energy  contained  in  protein  is  excreted  in 
urinar}^  sugar  and  20  per  cent,  of  that  contained  in  fat  is  elimin- 
ated in  the  unburned  y9-oxybutyric  acid. 

This,  then,  is  the  worst  picture  of  the  perverted  metabolism 
in  diabetes.  Sugar  can  not  bum,  fat  burns  only  as  far  as  /?-oxy- 
butyric  acid,  and  as  for  protein  a  part  of  its  amino-acids  are 
converted  into  sugar  and  another  part  into  /?-oxybutyric  acid, 
neither  of  which  can  be  burned. 

'  Magnus-Levy:    "Ergebnisse  d.  inn.  Med.,"  1908,  Bd.  i,  p.  372 
'  Magnus- Levy:   Ibid.,  p.  385. 


296  SCIENCE    OF   NUTRITION. 

Rosenfeld  has  said  that  fat  can  burn  only  "in  the  fire  of 
carbohydrates."  But  this  is  not  true.  Mandel  and  the  writer, 
in  their  work  on  a  diabetic  with  a  D  :  N  ratio  of  3.65  to  i,  and  who 
had  no  tolerance  for  carbohydrates,  found  a  low  acidosis  as 
measured  by  a  maximum  excretion  of  2  grams  of  ammonia, 
no  /?-oxybutyric  acid,  and  a  maximum  of  0.8  gram  of  acetone 
per  day.  On  the  other  hand,  von  Noorden^  and  Magnus-Levy^ 
report  cases  in  which  there  was  a  considerable  excretion  of 
acetone  bodies  in  the  urine  when  carbohydrates  were  burned. 
For  example,  one  patient  eliminated  4.9  grams  of  /?-oxybutyric 
acid  on  a  day  when  40  grams  of  starch  were  ingested  and  burned. 
There  are  great  individual  variations.  Thus,  Staubli^  reports 
concerning  a  diabetic  man  whose  ordinary  mixed  diet  was 
changed  to  one  of  meat  and  fat,  including  50  grams  of  bread, 
the  whole  containing  3200  calories.  After  ten  days  of  this  diet, 
during  which  the  sugar  output  remained  nearly  constant  at 
100  grams,  the  /?-oxybutyric  acid  fell  from  37.5  grams  daily  to 
nothing.  In  commenting  on  his  results  Staubli  says:  "The 
important  factor  which  causes  a  more  serious  condition  in  the 
metabolism  of  a  diabetic  is  the  quantity  in  which  carbohydrate 
is  administered  in  excess  of  the  tolerance  for  sugar.  Damage 
caused  by  a  continual  overworking  of  the  sugar-burning  capacity 
plays  a  large  part  in  the  progress  of  the  disease.  The  consid- 
erable withdrawal  of  carbohydrates  from  the  diet,  even  in  cases 
of  severe  diabetes  with  high  acidosis,  exerts  an  extraordinarily 
beneficial  influence.  This  can  be,  in  part,  explained  by  the 
increased  ability  to  burn  sugar  on  account  of  the  conservation 
of  the  body's  power  in  this  direction.  The  improvement  in  the 
capacity  for  sugar  combustion  exerts  on  its  side  a  beneficial 
action  on  the  acidosis." 

The  damage  done  in  severe  diabetes  by  flooding  the  organism 
with  carbohydrates  is  illustrated  by  the  fate  of  a  diabetic  in- 

^  Von  Noorden:   "Pathologie  des  Stoffwechsels,"  1907,  Bd.  ii,  p.  77. 
^  Magnus-Levy:   "Ergebnisse  d.  inn.  Med.,"  1908,  Bd.  i,  p.  404. 
^  Staubli:   "Deutsch.  Arch.  f.  klin.  Med.,"  1908,  Bd.  cxiii,  p.  125. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.    297 

dividual  who  had  been  kept  on  a  restricted  diet  at  the  advice 
of  the  writer,  but  on  the  recommendation  of  a  consultant  was 
given  a  large  quantity  of  carbohydrate;  this  resulted  in  onset 
of  coma,  which  proved  fatal. 

The  great  individual  variations  as  regards  the  presence  of 
the  acetone  bodies  seem  to  warrant  the  opinion  which  the  writer 
expressed  in  a  discussion  on  acidosis  at  Washington  inigo;,  that 
one  may  assume  the  existence  of  a  specific  /3-oxybutyric  acid 
ferment  analogous  to  the  ferment  which  breaks  down  the  sugar. 
Such  a  ferment  would  split  /?-oxybutyric  acid,  thereby  perform- 
ing one  of  the  last  offices  of  cleavage  of  the  fatty  molecules. 
Injury  to  this  ferment  may  be  complete  or  partial  even  as  in  the 
case  of  the  sugar  ferment,  but  damage  to  one  does  not  necessarily 
involve  proportionate  damage  to  the  other. 

The  elimination  of  /3-oxybutyric  acid  from  the  system  is 
furthered  by  the  administration  of  alkalis.  Staubli  reports  a 
diabetic  who  eliminated  34  grams  of  ^-oxybutyric  acid  daily 
when  the  diet  contained  60  grams  of  sodium  bicarbonate. 
This  excretion  fell  to  17  grams  on  a  diet  which  was  free  from 
alkali,  and  then  rose  to  45.2  grams,  on  return  to  60  grams  of 
bicarbonate.  Such  treatment  with  alkali  is  highly  beneficial, 
for,  as  Magnus-Levy  observes,  the  diabetic  does  not  die  in  coma 
because  of  the  neutralized  acid  which  is  eliminated  in  the  urine, 
but  rather  on  account  of  that  which  is  retained  in  the  body  which 
neutralizes  the  alkalis  of  tissue  and  of  body  fluids. 

Von  Noorden^  reports  cases  of  diabetics  who  have  excreted 
5  to  6  grams  of  acetone  and  30  to  40  grams  of  /?-oxybutyric  acid 
in  a  day,  and  yet  have  lived  comfortably  for  years. 

Minkowski^  noted  that  the  livers  of  his  depancreatized  dogs 
were  free  from  glycogen,  and  this  fact  has  been  confirmed  by 
other  observers.  He  also  found  that  when  levulose  was  given, 
glycogen  could  be  stored.    The  glycogenic  function  is  inhibited 

'Von  NoorfJen:  Von  Leyden's  "Handbuch  der  Ernahrungsthcrapie," 
1904,  Bd.  ii,  p.  253. 

*  Minkowski :  La)C.  cit. 


298  SCIENCE   or   NUTRITION. 

in  so  far  as  glycogen  production  from  dextrose  is  concerned,  but 
it  is  not  destroyed  as  regards  levulose  and  galactose.  This 
relation  may  simply  indicate  that,  perhaps  through  some  prop- 
erty of  the  liver,  glycogen  is  not  formed  from  dextrose  when 
dextrose  is  needed  for  the  tissues.  The  livers  of  human  beings 
who  have  died  of  diabetes  contain  little  or  no  glycogen,  though 
here  the  results  are  not  so  significant  as  in  dogs,  because  of 
hunger  and  suffering  which  may  precede  natural  death  in  this 
disease.^ 

The  present  discussion  of  metabolism  in  diabetes  has  been 
principally  directed  along  lines  involving  the  most  intense  forms, 
where  the  ability  to  burn  sugar  is  totally  absent.  It  has  been 
observed  that  there  are  many  intermediary  stages  in  this  disease 
in  which  the  power  to  burn  dextrose  is  very  different.  To 
determine  the  intensity  of  diabetes.  Von  Noorden  has  pre- 
pared a  standard  test-diet  which  is  largely  employed  in  Ger- 
many. This  diet  is  divided  into  portions  for  three  meals.  At 
breakfast  and  at  lunch  fifty  grams  of  bread  are  allowed.  The 
other  nutrients  are  meat,  eggs,  bacon,  butter,  green  vegetables, 
cheese,  lettuce  salad,  coffee,  and  wine.  Should  the  urine  of 
the  diabetic  be  free  from  sugar  on  such  a  diet,  the  diabetes  is 
mild  in  character.  More  bread  may  then  be  added  to  the  diet 
from  time  to  time  and  the  commencement  of  sugar  excretion  in 
the  urine  watched.  When  sugar  appears  the  limit  of  tolerance 
for  carbohydrate  has  been  reached.  If,  however,  the  urine 
contains  sugar  on  the  above  test-diet,  the  quantity  of  bread  is 
reduced,  and  the  urine  may  then  become  free  from  sugar. 
If  the  urine  contains  sugar  after  all  the  bread  has  been  removed 
from  the  diet,  the  case  is  one  of  severe  diabetes.  Even  here  the 
sugar  may  disappear  from  the  urine  on  reducing  the  protein  in 
the  diet  and  thereby  cutting  down  one  supply  of  carbohydrate. 
A  diabetic  of  this  order  may  live  on  a  low  protein  dietary  with 

^  Literature  by  Magnus-Levy:  Oppenheimer's  "Handbuch  der  Biochemie," 
1909,  Bd.  iv,  I,  p.  357. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.    299 

enough  fat  to  furnish  sufficient  energy  for  his  body's  require- 
ment, even  as  a  normal  man  may  exist. 

Mandel  and  Lusk^  have  commended  another  method  for  the 
clinical  examination  of  severe  types  of  diabetes,  using  the  D  :  N 
ratio  for  this  purpose.  The  procedure  is  as  follows :  If  a  diabetic 
be  given  a  meat-fat  diet  (rich  cream,  meat,  butter,  and  eggs) 
and  the  twenty-four  hour  urine  of  the  second  day  be  properly 
collected,"  the  discovery  of  3.65  grams  of  dextrose  to  one  gram 
of  nitrogen  signifies  a  complete  intolerance  for  carbohydrates 
and  probably  a  quickly  fatal  outcome.  The  authors  called  this 
(D  :  N  ::  3.65  :  i)  the  fatal  ratio. 

A  lower  ratio  of  dextrose  to  nitrogen  on  this  diet  indicates 
that  some  protein  sugar  may  be  burned.  Such  a  tolerance  for 
sugar  may  be  increased  on  a  meat-fat  diet  so  that  the  D  :  N  ratio 
falls,  and  in  favorable  cases  the  dextrose  may  entirely  disappear 
from  the  urine. 

In  the  case  of  the  medical  student  of  Mandel  and  Lusk,  the 
ratio  was  constantly  3.65  :  i  and  the  progress  of  the  disease  rapid- 
ly fatal,  death  occurring  six  weeks  after  the  ratio  was  discovered. 
In  another  case  of  the  same  investigators,  a  diabetic  was  re- 
vived from  coma  with  sodium  bicarbonate;  then,  after  two 
days,  the  meat-fat  diet  was  given.  On  the  second  day  of 
this  diet  the  D  :  N  ratio  was  2.91  :  i;  on  the  tenth  day,  0.34  :  i; 
on  the  twenty-third  day  the  patient's  urine  was  free  from  sugar 
and  he  was  eating  a  small  amount  of  carbohydrate.  This  is  an 
illustration  of  improving  tolerance  when  a  diabetic  is  placed  on 
a  diet  which  is  free  from  carbohydrates.  Good  practice  calls 
for  the  occasional  interpolation  of  periods  in  which  the  dietary 
is  free  from  carbohydrates,  on  account  of  the  beneficent  effect 
on  the  power  of  the  diabetic  to  burn  sugar. 

'Mandel  and  Lusk:  "Dcutsches  Archiv  fur  klinische  Medizin,"  1904, 
Bd.  Ixxxi,  p.  472. 

'  The  urine  should  be  collected  so  that  an  early  morning  hour  (before  break- 
fast) terminates  the  period  for  one  day.  This  is  necessary  because  the  dex- 
trose arising  from  ingested  protein  is  eliminated  before  the  nitrogen  belonging 
to  the  same  (p.  130).  The  long  period  ijctween  the  evening  meal  and  break- 
fast allows  for  the  elimination  of  both  constituents. 


300  SCIENCE   OF   NUTRITION. 

The  above-mentioned  individual  appeared  to  be  doing 
well,  two  years  after  the  test,  but  had  to  look  carefully  to  his 
dietary.  His  D  :  N  ratio  after  one  week  of  a  strict  meat  and 
fat  diet  was  2.8  :  i,  which  indicated  a  less  favorable  outlook  than 
two  years  before.  He  had  not  lost  in  weight  and  went  about 
his  usual  occupation.     A  year  later  he  died  in  coma. 

Physicians  will  object  to  this  manner  of  investigation  be- 
cause there  is  no  ready  method  of  determining  the  nitrogen  in 
the  urine.  With  the  growth  of  laboratories  for  medical  work, 
this  difficulty  will  be  removed.  A  frequent  source  of  error  is 
the  untrustworthiness  of  the  ordinary  diabetic  patient,  who 
will  privately  eat  carbohydrate  in  spite  of  the  physician's  pro- 
hibition. 

Having  discovered  by  investigation  the  tolerance  of  a  dia- 
betic for  carbohydrates,  the  next  step  is  to  see  that  the  patient 
is  supplied  with  a  sufi&cient  amount  of  energy  in  the  food  to 
correspond  with  the  requirement  of  his  organism  (35  calories 
per  kilogram).  A  diabetic  with  no  tolerance  for  carbohydrates 
will  require  between  200  and  250  grams  of  fat  according  to  his 
weight.  This  amount  will  not  be  taken  unless  all  the  devices  of 
variation  in  flavor  be  made  use  of.  The  patient  will  not  take  it 
of  his  own  accord,  and  the  amount  required  should  be  carefully 
allotted,  preferably  in  a  sanatorium.  Diabetics  can  be  educated 
in  such  establishments  to  a  proper  course  of  dieting  which  is  the 
only  hope  for  the  amelioration  of  their  troubles.  Alcohol  may 
be  used,  in  part,  to  furnish  the  necessary  calories  in  the  diet. 
Benedikt  and  Torok^  were  able  to  reduce  the  acetone  excretion, 
as  well  as  that  of  nitrogen  and  dextrose,  after  administering  al- 
cohol to  a  diabetic.  Staubli,^  however,  states  that  alcohol  may 
in  some  cases  reduce  the  tolerance  of  the  diabetic  for  carbo- 
hydrate. 

There  is  no  known  cure  for  diabetes.  There  is  nothing 
except  dieting  that  affords  permanent  relief.     Opium  is  said  to 

1  Benedikt  and  Torok:    "  Ztschr.  f.  klin.  Med.,"  1906,  Bd.  Ix,  p.  329. 
^Staubli:    "Deutsch.  Arch.  f.  klin.  Med.,"  1908,  Bd.  cxiii,  p.  125. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.   301 

reduce  the  sugar  output  in  cases  bordering  on  the  severe  type.^ 
The  cause  of  this  action  is  unkno\\Ti.  Experiments  inaugurated 
upon  an  individual  having  the  3.65  :  i  ratio  might  indicate 
v^'hether  its  effect  was  really  to  increase  the  combustion  of  sugar 
or  only  to  reduce  the  general  metabolism.  The  ingestion  of  ex- 
tracts of  different  organs  does  not  apparently  influence  the  sugar 
excretion.  Laboratory  investigations  of  the  glycolytic  power  of 
pancreas  extracts  have  been  very  numerous,  but  have  failed  to 
give  striking  results.  It  is  possible  that  the  supposed  enzyme 
or  activating  substance  is  extremely  sensitive  to  a  change  in 
normal  conditions.  Mandel  and  Lusk  gave  large  quantities 
of  yeast  to  a  diabetic  man  without  changing  the  D  :  N  ::  3.65  :  i, 
which  shows  that  the  enzymes  of  yeast  are  not  able  to  penetrate 
the  intestinal  wall  so  that  they  may  replace  the  natural  ferment 
of  the  organism. 

Minkowski^  discovered  that  levulose  largely  reduced  protein 
metabolism  in  the  case  of  depancreatized  dogs.  This  led  to  the 
widespread  use  of  levulose  in  diabetes.  Mandel  and  Lusk, 
however,  found  that  the  increase  of  sugar  in  the  urine  of  their 
diabetic  man,  after  giving  100  grams  of  levulose,  was  80  per 
cent,  of  the  sugar  ingested.  The  levulose  had  no  effect  what- 
ever on  protein  metabolism. 

Von  Noorden^  confirms  this  observation.  He  also  states 
that  in  severe  cases  of  diabetes,  le\ailose  appears  in  the  urine. 
He  believes  that  levulose  is  normally  produced  in  metabolism 
and  is  normally  burned.  In  very  rare  cases  called  levulosuria, 
le\ailose  alone  appears  in  the  urine.  One  case  of  complete 
intolerance  for  levulose  has  been  reported.^  Very  likely  in  Min- 
kowski's depancreatized  dogs  the  power  of  oxidizing  levulose 
was  entirely  normal. 

The  negativ^e  results  as  regards  the  value  of  levulose  were 

'  Von  Noorden:  "Diabetes,"  1905,  p.  158. 

*  Minkowski:  hoc.  cit.,  p.  131. 

'Von  Noorden:  Loc.  cit.,  p.  50. 

*Neuh)auer:   "Miinchcner  med.  Wochenschrift,"  1905,  p.  1523. 


302  SCIENCE    OF   NUTRITION. 

especially  interesting  in  the  case  of  Mandel  and  Lusk.  This 
diabetic  medical  student  was  confident  of  the  efficacy  of  levu- 
lose  on  account  of  opinions  expressed  by  the  writer  in  his  lec- 
tures. On  the  days  of  levulose  ingestion  the  patient's  spirits 
revived,  his  strength,  measured  on  the  ergograph,  decidedly 
improved  and  his  companions  remarked  upon  the  benefit  re- 
ceived. All  of  vv^hich  shows  that  subjective  sensations  are  not 
to  be  used  as  scientific  criteria.  Staubli^  states  that  adminis- 
tration of  levulose  reduces  the  diabetic's  tolerance  for  dextrose. 

For  the  therapeutics  of  diabetes  in  greater  detail  the  reader 
is  referred  to  other  sources.^ 

In  this  connection  it  may  be  mentioned  that  (/-glucuronic  acid 
and  pentoses  have  a  bearing  on  carbohydrate  metabolism.  A 
large  variety  of  substances  (camphor,  chloral,  turpentine)  form 
syntheses  with  glucuronic  acid  in  the  organism,  and  correspond- 
ing glucuronates  are  then  eliminated  in  the  urine.  At  first 
glance  glucuronic  acid  appears  to  be  the  preliminary  oxidation 
product  of  glucose,  as  is  suggested  by  the  following  equation: 

OCH(CHOH)4CH20H  +  O^  =  OHC(CHOH)4COOH  +  H^O 
Dextrose.  Glucuroaic  acid. 

However,  Mandel  and  Jackson^  administered  camphor  to 
fasting  dogs  for  several  days  and  noted  the  excretion  of  glucu- 
ronic acid.  On  giving  large  quantities  of  dextrose  the  protein 
metabolism  fell  and  with  it  the  glucuronic  acid  elimination;  and 
on  giving  the  animal  chopped  meat  the  quantity  of  campho- 
glucuronic  acid  in  the  urine  was  correspondingly  increased.  It 
may  be  safely  inferred  that  glucuronic  acid  is  produced  solely 
in  the  intermediary  metabolism  of  protein.     For  the  large  liter- 

^  Staubli:   "Deutsches  Arcliiv  ftir  klin.  Med.,"  1908,  Bd.  cxiii,  p.  125. 

^  Falta:  "Ergebnisse  der  innere  Medizin,"  1908,  Bd.  ii,  p.  74;  Falta:  Harvey- 
Society  Lecture,  "Archives  of  Internal  Medicine,"  1909,  vol.  iii,  p.  159;  Janeway: 
"Am.  Journal  of  the  Medical  Sciences,"  1909,  vol.  cxxxvii,  p.  313. 

*  Mandel  and  Jackson:  "American  Journal  of  Physiology,"  1902,  vol.  viii. 
Proceedings  of  the  American  Physiological  Society,  p.  xiii. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.   303 

ature  on  this  subject,  and  also  on  the  pentoses,  the  reader  is 
referred  to  other  sources.^ 

Pentoses,  ^Yhich  are  sugars  containing  five  atoms  of  carbon, 
have  been  detected  in  animal  and  vegetable  tissue.  Hammar- 
sten  found  a  pentose  in  the  nucleoprotein  of  the  pancreas. 
Neuberg  showed  that  this  pentose  and  the  one  obtained  from 
nucleoprotein  in  the  liver  is  /-xylose.  Grund^  has  found  pen- 
toses in  all  organs  of  the  body,  particularly  in  those  rich  in 
nuclear  material. 

Salkowski  and  Neuberg  have  shown  that  /-xylose  may  be 
derived  through  ferment  action  on  c?-glucuronic  acid.  Salkow- 
ski was  the  first  to  detect  a  pentose  in  the  urine,  and  this  Neu- 
berg has  sho^^^l  to  be  ^-arabinose.  The  elimination  of  pentoses 
in  the  urine  may  accompany  diabetes,  but  in  extremely  rare 
cases  a  simple  pentosuria  occurs  in  which  pentose  is  the  only 
sugar  appearing  in  the  urine. 

Luzzatto^  reports  such  a  case  in  which  the  elimination  of 
arabinose  was  independent  of  diet  or  mental  or  muscular  effort. 
Luzzato  believes  the  pentose  in  this  case  to  have  been  /-arab- 
inose. Neuberg  finds  that  in  the  normal  rabbit  /-arabinose  is 
more  readily  burned  than  (f-arabinose.  Luzzato's  case  could 
be  explained  by  supposing  that  the  body  had  lost  its  normal 
power  to  burn  /-arabinose  as  normally  produced  in  metabolism. 

Pentosuria  is  occasionally  discovered  in  the  routine  of  life 
insurance  examinations.  So  far  as  is  known  it  does  not  indi- 
cate danger  to  general  health. 

Cremer,^  in  a  series  of  excellent  experiments,  has  shown  that 
a  vegetable  pentose,  such  as  rhamnose,  may  be  burned  in  a 
rabbit  and  spare  an  isodynamic  equivalent  of  fat.  In  one  rabbit, 
on  a  fasting  day,  the  total  metabolism  amounted  to  129.1  cal- 
ories (protein,  22.5,  and  fat,  106.6),  and  on  the  day  when  rham- 

>  Neuberg:  "Ergcbnisse  der  Physiologic,"  1904,  Bd.  iii,  i  Abtheilung,  p.  373. 
*Grund:    "Zeitschrift  fiir  physioiogische  Chemie,"  1902,  Bd.  xxxv,  p.  iii. 
'Luzzatto:   "Hofmeister's  Bcitrage,"  1904,  Bd.  vi,  p.  87. 
*  Cremer:    "Zeitschrift  fur  Biologic,"  1901,  Bd.  xlii,  p.  428. 


304 


SCIENCE   OF   NUTRITION. 


nose  was  given  to  128.4  calories  (protein,  21.36;  fat,  32.9,  and 
rhamnose,  74.11). 

Lindemann  and  May^  found  that  90  grams  of  rhamnose 
could  be  used  by  a  normal  man.  When,  however,  rhamnose  was 
given  to  a  diabetic  individual  whose  urine  had  been  sugar-free, 
sugar  appeared  in  the  urine.  In  cases  of  severe  diabetes  re- 
ported by  von  Jacksch^  it  was  found  that  rhamnose,  arabinose, 
and  xylose  tended  to  increase  the  protein  metabolism,  and  hence 
the  sugar  output,  and  also  brought  about  diarrhea.  The  use 
of  pentoses  in  diabetes  has  therefore  not  been  successful.  The 
pentoses  rhamnose,  arabinose,  and  xylose  are  not  convertible  into 
dextrose  in  the  organism.^ 

Opie*  has  endeavored  to  establish  a  connection  between 
changes  in  the  islands  of  Langerhans  of  the  pancreas  and  the 
cause  of  diabetes.  Jane  way  and  Oertel,^  von  Noorden,  and 
others,  have  reported  autopsies  on  cases  of  severe  diabetes  in 
which  the  pancreas  appeared  perfectly  normal.  It  is  not  always 
possible  to  observe  with  the  microscope  the  cause  of  patho- 
logical change  in  function. 

On  autopsy  in  diabetes  large  quantities  of  fat  are  frequently 
found  in  the  liver  and  muscles.  The  same  is  observed  in 
chloroform  narcosis  when  sugar  appears  in  the  urine,  in  anemia, 
and  after  respiration  of  rarefied  air,  where  lactic  acid  is  elimin- 
ated in  the  urine  (p.  256),  and  in  phosphorus-  and  arsenic- 
poisoning,  in  acute  yellow  atrophy,  in  pernicious  vomiting  of 
pregnancy,  in  eclampsia  and  in  cyclic  vomiting  in  children, 
which  are  similarly  accompanied  by  an  elimination  of  lactic 
acid.  These  phenomena  are  always  associated  with  an  in- 
creased protein  metabolism  and  an  increased  ammonia  and 

^  Lindemann  and  May:  "Deutsches  Archiv  ftir  klin.  Med.,"  1896,  Bd.  Ivi, 
p.  282. 

^  Von  Jacksch:   Ihid.,  1899,  Bd.  Ixiii,  p.  612. 

^Brasch:    "Zeitschrift  fiir  Biologic, "  1907,  Bd.  1,  p.  113. 

*Opie:    "Journal  of  Experimental  Medicine,"  1901,  vol.  v,  p.  397. 

^  Janeway  and  Oertel:    "Virchow's  Archiv,"  1903,  Bd.  clxxi,  p.  547. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.   305 

amino-acid  output  in  the  urine/  Fat  likewise  appears  in  the 
mammary  glands  during  lactation  (p.  239). 

Virchow  assumed  a  fatty  degeneration  of  protein  in  which 
the  tissue  protein  was  converted  into  fat,  as  distinguished  from 
a  fatty  infiltration  in  which  body  fat  passed  into  the  cells. 
Much  of  the  earlier  wi'iting  of  Voit  is  pervaded  vdth  the  theory  of 
a  considerable  origin  of  fat  from  protein  (p.  142).  The  idea  of 
a  fatty  degeneration  of  protein  in  the  old  sense  has  been  largely 
overturned  by  the  work  of  Rosenfeld.^  Rosenfeld  finds  that  if 
a  dog  be  starved  and  then  given  sheep's  fat,  and  again  starved, 
the  ingested  fat  will  be  found  deposited  as  sheep's  fat  in  his 
adipose  tissue,  while  the  liver  will  contain  about  10  per  cent,  of 
fat,  and  this  characteristic  dog  fat.  If  now  phosphorus-  or 
phlorhizin-poisoning  be  induced  and  the  liver  be  examined,  40 
per  cent,  of  fat  may  be  found  therein,  and  this  in  the  form  of 
sheep's  fat.  Hence,  in  these  cases  the  fat  is  simply  transported 
to  the  liver  from  the  fat  deposits  of  the  body.  The  fat  in  the 
blood  is  largely  increased.^  The  fat  becomes  normal  in  quan- 
tity in  the  liver  twenty-four  hours  after  the  cessation  of  the  phlor- 
hizin  action.     It  is  retransported  to  the  places  of  fat  deposit. 

If  a  fatty  "degeneration"  were  to  be  found  anywhere,  it 
would  certainly  be  looked  for  in  the  dying  cells  of  the  phos- 
phorus liver,  or  in  the  analogous  condition  of  acute  yellow 
atrophy  of  the  liver.     But  another  explanation  avails. 

Mandel  and  Lusk*  have  shown  that  lactic  acid  disappears 
from  the  blood  and  urine  of  a  phosphorized  dog  if  phlorhizin 
glycosuria  be  induced.  The  writer  believes  that  the  lactic  acid 
which  occurs   is  derived  from  the  sugar  formed  in  protein 

'For  literature  consult  Ewing:  "Archives  of  Internal  Medicine,"  1908, 
vol.  ii,  p.  476. 

*  Rosenfeld:    "Ergebnisse  der  Physiologic,"  1903,  Bd.  ii,  I,  p.  50. 

'  B.  Fischer  ("Virchow's  Archiv,"  1903,  Bd.  clxxii,  pp.  30,218)  reports  a 
case  of  coma  diabeticum  in  which  the  blood  scrum  contained  23  per  cent,  of  fat. 
Klempercr  and  Umber  ("Zeitschrift  fur  klini.sche  Medizin,"  1908,  Bd.  Ixv,  p. 
340)  state  that  of  nine  diabetics  with  acidosis  seven  had  lipemia. 

*  Mandel  and  Lusk:  "American  Journal  of  Physiology,"  1906,  vol.  xvi,  p. 

129. 

20 


3o6  ,        SCIENCE   OF  NUTRITION. 

metabolism.  In  the  above  case  the  sugar  is  removed  without 
conversion  into  lactic  acid.  In  phlorhizin  diabetes,  dextrose 
does  not  burn ;  in  phosphorus-poisoning  lactic  acid  derived  from 
dextrose  does  not  burn.  In  both  cases  a  sugar-hungry  cell,  or 
one  where  carbohydrate  is  not  oxidized,  is  found,  and  under 
these  circumstances  fat  is  attracted  to  the  cell,  and  in  larger 
quantities  than  can  be  useful.  Wherever  sugar  freely  burns  this 
fatty  infiltration  is  impossible  (p.  i66).  A  reduced  local  circu- 
lation in  a  portion  of  the  heart  may  produce  anemia  of  the  part, 
an  imperfect  local  oxidation  of  lactic  acid  normally  formed, 
and  a  fatty  infiltration  of  the  locality.  The  writer  offers  this 
hypothesis  as  his  explanation  of  fatty  changes  in  tissue  in 
general. 

Present-day  medical  literature  is  frequently  influenced  by 
the  idea  of  a  reduced  general  oxidation  in  the  body.  Except 
in  the  case  of  myxedema  which  is  accompanied  by  a  fall  in  body 
temperature,  and  possibly  in  obesity,  no  such  condition  occurs. 
The  writer^  has  shown  that  in  phosphorus-poisoning,  the  clas- 
sical example  of  supposed  reduced  oxidation,  there  was  actually 
no  reduction  in  the  total  heat  production,  but  rather  an  increase 
due  to  a  slight  fever.  From  the  fourth  day  to  the  sixth  of  sim- 
ple fasting  in  one  dog  the  total  metabolism  for  twenty-four 
hours  averaged  45.2  calories  per  kilogram,  and  on  the  ninth 
day  to  the  eleventh  of  fasting  which  preceded  death  from  phos- 
phorus-poisoning the  heat  production  was  48.8  calories. 

It  is  therefore  evident  that  the  presence  of  lactic  acid  is 
only  a  symptom  in  the  group  of  diseases  just  mentioned  (p.  304) 
and  is  no  more  an  indication  of  a  reduction  in  oxidative  power 
as  represented  by  the  total  heat  production  than  is  the  elimina- 
tion of  sugar  in  diabetes.  The  abundant  ammonia  in  the  urine 
is  used  to  neutralize  the  acid  produced.  The  reduction  in  the 
amount  of  lactic  acid  oxidized  raises  the  total  protein  metabo- 
lism. The  deficient  deamination  which  results  in  the  elimina- 
tion of  amino-acids  in  the  urine  may  be  due  to  the  injury  of 

^Lusk:   "American  Journal  of  Physiology,"  1907,  vol.  xix,  p.  461. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.   307 

deaminating  enzymes  by  the  presence  of  lactic  acid;  or  it 
may  be  that  deamination  is  difficult  with  certain  amino-acids 
when  it  is  not  accompanied  by  oxidation  with  the  formation 
of  ketonic  acids  according  to  the  formula  given  on  p.  293;  or 
it  may  be  due  to  other  unkno^\'n  causes. 

It  has  been  stated  that  the  action  of  phosphorus  is  to  induce 
autolysis  (self-digestion)  of  the  body's  protoplasm  (Jacoby/ 
WaldvogeP),  since  leucin,  tyrosin,  glycocoll/  phenyl-alanin  and 
arginin*  and  other  amino-acids  may  be  eliminated  in  consider- 
able quantity  in  the  urine.  Wakeman^  finds  a  change  in  the 
relative  amounts  of  histidin,  arginin,  and  lysin  contained  in  the 
liver  substance  after  phosphorus-poisoning,  arginin  in  particu- 
lar being  reduced  below  the  quantity  found  in  the  liver  of  the 
normal  dog.  Oswald^  thinks  that  phosphorus  destroys  or 
weakens  the  antiautolytic  agents  of  the  body.  That  autolytic 
enzymes  do  not  gain  free  control  over  the  cells  through  the  di- 
rect influence  of  phosphorus  is  proved  by  the  work  of  Ray, 
McDermott,  and  Lusk.''  These  authors  found  that  phosphorus 
injections  raised  the  protein  metabolism  of  fasting  dogs  to  250, 
260,  283,  248,  183,  and  164  per  cent,  of  that  of  the  dog  when 
normal.  They  contrasted  this  increased  protein  metabolism 
with  that  obtained  in  phlorhizin  glycosuria,  which  is  represented 
by  increases  to  540,  450,  340,  and  340  per  cent.  \ATien,  how- 
ever, they  gave  phlorhizin  and  obtained  the  increased  metabol- 
ism, and  then  injected  phosphorus,  this  was  not  followed  by  any 
marked  increase  in  protein  metabolism.  Under  these  circum- 
stances phlorhizin  glycosuria  is  the  predominating  factor,   re- 

'  Jacoby:    "Zeitschrift  fiir  physiologische  Chemie,"  1900,  Bd.  xxx,  p.  174. 
^  Waldvogel:   "Archiv  fiir  klinische  Medizin,"  1905,  Bd.  Ixxxii,  p.  437. 
'  Abderhalden  and  Bergell:    "Zeitschrift  fiir  physiologische  Chemie,"  1903, 
Bd.  xxxix,  p.  464. 

*  Wolgemuth:  Ibid.,  1905,  Bd.  xliv,  p.  74. 

*Wak.eman:    "Zeitschrift  fiir  physiologische  Chemie,"  1905,  Bd.  xhv,  p. 

•Oswald:    " Biochemisches  Centralblatt,"  1905,  Bd.  iii,  p.  365. 
^  Ray,  McDermott,  and  Lusk:    "American  Journal  of  Physiology,"  1899, 
vol.  iii,  p.  139. 


3o8  SCIENCE   OF   NUTRITION. 

moving  the  dextrose  produced  from  protein  before  it  could  be 
converted  into  lactic  acid.  In  this  connection  it  may  be  stated 
that  Laquer  ^  finds  no  evidence  of  autolysis  in  the  fresh  livers 
of  dogs  which  have  died  of  acute  arsenical  poisoning,  nor  was 
the  rate  of  autolysis  in  these  livers  in  any  way  accelerated,  an 
effect  said  by  Jacoby  to  be  characteristic  of  the  livers  of  dogs 
which  have  died  of  phosphorus-poisoning.  It  seems  therefore 
desirable  to  accept  with  caution  this  modern  opinion  which 
holds  that  in  diseases  such  as  those  caused  by  metallic  poisons 
where  high  protein  metabolism  is  found  there  must  of  necessity 
be  autolysis  (or  a  condition  in  which  proteolytic  enzymes  run 
riot)  within  the  living  protoplasm. 

As  regards  phosphorus-poisoning  Araki^  believes  that  lactic 
acid  accumulation  is  due  to  lack  of  oxygenation  of  the  tissues 
caused  by  a  slow  heart-beat,  but  not  due  to  anemia.  He  does 
not  believe  the  oxygen  deprivation  to  be  very  pronounced.  The 
writer  offers  the  explanation  that  phosphorus  may  affect  the 
enzyme  which  breaks  up  the  lactic  acid  derived  from  dextrose, 
and  the  accumulation  of  this  acid  may  prevent  the  action  of 
some  of  the  deaminating  enzymes;  and,  further,  its  non-com- 
bustion may  necessitate  an  increase  of  protein  metabolism. 

This  theory  is  strengthened  by  the  discovery  of  Schryver^ 
that  the  addition  of  lactic  acid  favors  the  accumulation  of 
amino-acids  in  autolysis  of  the  liver. 

Claude  Bernard  showed  that  dextrose,  whether  derived  from 
protein  or  starch,  was  convertible  into  glycogen,  and  this  again 
was  changeable  into  dextrose.  Present  knowledge  adds  lactic 
acid  to  both  ends  of  this  chain  in  showing  the  following  possible 
progression  of  events— lactic  acid,  dextrose,  glycogen,  dextrose, 
lactic  acid. 

Quite  pertinent  to  this  theoretical  discussion  is  the  obser- 

^  Laquer:    "  Zentralblatt  fur  Physiologic,"  1909,  Bd.  xxiii,  p.  717. 
^Araki:    " ' Zeitschrif t  fiir  physiologische  Chemie,"  1892,  Bd.  xvii,  p.  337. 
^  Schryver:    "The  Bio-Chemical  Journal,"  1906,  vol.  i,  p.  153. 


METABOLISM  IN  DIABETES  AND  PHOSPHORUS-POISONING.   309 

vation  of  von  Jaksch^  on  a  patient  who  recovered  from  phos- 
phorus-poisoning, and  in  whom  a  desire  for  carbohydrates 
marked  the  beginning  of  convalescence. 

It  should  also  be  noted  (see  p.  i8o)  that  more  carbohydrates 
must  be  ingested  in  cases  of  hepatic  disease  to  maintain  nitrogen 
equilibrium  than  are  required  in  health.^ 

Regarding  the  normal  destruction  of  dextrose  Buchner  and 
Meisenheimer^  give  the  following  picture  of  the  production  of 
lactic  acid  from  it  by  hydrolytic  changes. 


CHO 

I 
CHOH 

I 
CHOH 

CHOH 

CHOH 

I 
CH2O 

Dextrose. 


OH 
OH 

H 
H 

— > 
OH 
OH 

H 
H 


COOH 

COOH 

1 

CHOH 

CHOH 

CH2 
CO 

H 

> 

OH 

CH3 
COOH 

CHOH 

CHOH 

1 

CH3 

1 
CH3 

Hypothetical 

intermediary 

product. 

Lactic  acid. 

The  next  step  in  the  process  is  conjectural.  Buchner  be- 
lieves that  alcohol  is  formed.  Walter  Lob*  suggests  that  lactic 
acid  may  be  converted  into  acetol,  CH3  CO  COOH,  and  then 
into  formaldehyde,  which  latter  is  reconvertible  into  dextrose 
by  the  liver  (p.  277).  Or  one  may  accept  the  idea  of  Magnus- 
Levy/  who  found  that  if  sugar  were  digested  with  aseptic  liver 
tissue  lactic  acid,  acetic  acid,  and  butyric  acid  were  formed  with 
the  evolution  of  hydrogen.  The  interpretation  to  be  placed  on 
this  is  that  lactic  acid  yields  acetic  aldehyde  and  formic  acid  as 
follows : 

'  Von  Jaksch:   "Zcitschrift  fur  physiologischc  Chemie,"  1903,  Bd.  x\,  p.  123. 
^Tallquist:    "Archiv  fur  Hygiene,"  1908,  Bd.  Ixv,  p.  39. 
^  Buchner  and  Meisenheimer:   "  Berichtc  d.  d.  chem.  Gescllschaft,"  1904, 
Bd.  xxxvii,  p.  417. 

*Lob:    "Biochemische  Zeitschrift,"  1908,  Bd.  xii,  p.  85. 
*  Magnus-Levy :   "Archiv  fiir  Physiologic,"  1902,  p.  365. 


3IO  SCIENCE   OF  NUTRITION. 

CH3  CH3 

CHOH       >       CHO 


COOH  HCOOH 

Lactic  acid.  Acetic  aldehyde  and 

formic  acid. 

The  acetic  aldehyde  might  then  be  oxidized  or  it  might  be 
condensed  into  aldol,  which  is  /?-oxybutyric  aldehyde.  From 
this  butyric  acid  may  arise,  and  with  a  larger  number  of  acetic 
aldehyde  molecules  higher  and  higher  fatty  acids  might  be 
S}Tithesized. 

This  chemical  basis  for  the  formation  of  fat  from  a  product 
of  dextrose  metabolism  may  thus  be  written : 


CH3 

CH3 

H 

CH3 

CHO 

— > 

CHOH 

H 
> 

CHj 

CH3 

CH2 

CHj 

CHO 

CHO 

0 

COOH 

lie  aldehyde. 

Aldol. 

Butyric  acid. 

Remembering  former  statements  one  sees  an  interesting 
play  of  the  cells  upon  the  molecule  of  lactic  acid.  At  one  time 
it  is  synthesized  to  sugar,  at  another  it  is  broken  down  to  form 
acetic  aldehyde  and  this  synthesized  to  higher  fatty  acid.  When 
the  system  is  flushed  with  carbohydrate  and  the  glycogen  re- 
positories are  charged  with  it,  then  one  might  picture  the  break- 
ing up  of  carbohydrate  into  lactic  acid  and  this  to  acetic  aldehyde 
and  formic  acid,  a  condition  in  which  the  energy  of  the  cell 
might  be  provided  from  the  plentiful  supply  of  formic  acid  while 
the  acetic  aldehyde  molecules  were  condensed  to  form  higher 
fatty  acids. 


CHAPTER  XIII. 
METABOLISM  IN  FEVER, 

By  fever  is  generally  understood  a  complex  of  phenomena 
the  dominant  characteristic  of  which  is  a  rise  of  body  tempera- 
ture. If  the  term  fever  be  confined  simply  to  the  latter  aspect, 
one  might  classify  fevers  as  follows: 

(i)  Physiological  fever,  induced,  for  example,  by  immersion 
in  a  hot  bath  at  a  temperature  of  40°,  which  prevents  the  normal 
loss  of  body  heat  through  radiation  and  conduction.  (2)  Neu- 
rogenic fever,  as  brought  about  by  the  direct  stimulation  of 
nerve-cells  in  the  corpora  striata  of  the  mid-brain.  (3)  Non- 
infective  surgical  fever,  commonly  called  aseptic  fever,  due  to 
the  resolution  of  blood-cells  or  crushed  tissue  in  the  organism. 
(4)  Infective  fever,  produced  after  the  infection  of  the  organism 
by  certain  bacteria  or  their  products  and  by  some  protozoa. 
Or,  one  may  consider  fever  as  being  due  to  infection  by  bacteria 
or  protozoa,  and  include  all  other  increases  of  temperature 
under  the  term  of  hyperthermia. 

In  a  previous  chapter  the  mechanism  of  normal  heat  regu- 
lation has  been  explained.  It  was  there  noted  that  on  a  warm, 
moist  day  the  temperature  of  a  fat  individual,  when  he  was 
working  hard,  rose  considerably  above  the  normal.  This  effect, 
if  carried  to  an  extreme,  results  in  " sunstroke,^^  where  the  over- 
heating of  the  body  causes  a  rapid  pulse,  accompanied  by  dizzi- 
ness, delirium,  or  unconsciousness.  But  in  the  great  majority 
of  cases  the  body  temperature  remains  delicately  balanced, 
notwithstanding  changes  in  outside  environment,  or  internal 
heat  production.  In  the  fat  person  at  hard  work  the  condition 
of  increased  metabolism  is  combined  with  that  of  difficult  dis- 
charge of  heat.     A  person  placed  in  a  bath  at  40°  would  be  sub- 

3" 


312  SCIENCE   OF   NUTRITION. 

ject  to  conditions  where  there  could  be  no  heat  loss,  but  rather 
a  gain  in  heat,  even  though  his  metabolism  were  low.  In  a 
normal  person,  therefore,  a  rise  in  temperature  may  be  due  to 
increased  heat  production,  with  difficulty  in  discharging  it,  or 
a  check  of  heat  loss  may  be  the  only  factor  of  the  higher  tem- 
perature. In  the  discussion  of  fever  one  must  consider  two 
possible  causes:  (i)  an  increase  in  heat  production,  and 
(2)  a  decrease  in  the  facilities  for  the  discharge  of  heat  produced. 

It  has  already  been  set  forth  that  the  metabolism  in  a  cold- 
blooded animal  increases  with  the  temperature  of  his  environ- 
ment. Warmed  tissue  metabolizes  more  material  than  cooled 
tissue.  It  is  therefore  to  be  expected  that  the  metabolism  in  an 
organism  which  has  been  warmed  to  fever  heat  will  be  greater 
than  the  normal.  This  was  beautifully  shown  in  the  experi- 
ments of  Pfiiiger,^  who  subjected  both  curarized  and  normal 
rabbits  to  external  warmth  which  raised  their  temperatures. 
In  the  animals  whose  voluntary  muscles  were  paralyzed  by 
curare,  as  the  rectal  temperature  rose  from  39°  to  41°,  the  oxy- 
gen absorption  increased  10  per  cent,  for  each  degree  of  tem- 
perature increase.  In  the  normal  animals  the  increased  me- 
tabolism between  temperatures  of  38.6°  and  40.6°  was  shown 
by  increases  of  5.7  per  cent,  for  oxygen,  and  6.8  per  cent,  for 
carbon  dioxid  for  a  rise  of  one  degree  of  temperature. 

It  has  been  noted  in  another  chapter  (p.  102)  that  Rubner 
found  in  man  that  a  bath  at  a  temperature  of  35°  had  no  effect 
on  metabolism,  while  one  at  44°  increased  the  volume  of  respira- 
tion 18.8  per  cent.,  the  oxygen  absorption  17.3  per  cent.,  and 
the  carbon  dioxid  elimination  32.1  per  cent.  Linser  and  Schmid^ 
confirm  these  results  in  experiments  on  two  men  suffering  from 
ichthyosis  hystrix,  which  involved  almost  complete  loss  of  func- 
tion of  the  sweat  glands.  The  body  temperature  of  these  men 
could  be  varied  by  altering  the  temperature  of  their  living-room 

^Pfliiger:   "Pfliiger's  Archiv,"  1878,  Bd.  xviii,  pp.  303,  356. 
2  Linser  and  Schmid:   "Archiv  fiir  klinische  Medizin,"  1904,  Bd.  Ixxix,  p. 
514. 


METABOLISM   IN   FEVER.  313 

between  30°  and  38°.  The  humidity  of  the  room  was  from 
40  to  50  per  cent.  The  maximum  increase  in  the  metaboHsm 
of  these  individuals  is  represented  by  a  rise  in  carbon  dioxid 
excretion  from  3.8  c.c.  per  minute  and  kilogram  at  the  body 
temperature  of  36.2°  to  5.3  c.c.  per  minute  and  kilogram  at  39°. 
The  number  of  respirations,  which  were  from  1 2  to  1 5  per  minute 
at  36°,  increased  to  20  and  22  at  39°.  The  total  increase  in  the 
carbon  dioxid  output,  due  to  a  rise  of  3°  through  simple  warming 
of  cells,  amounted  to  40  per  cent. 

The  next  question  is  of  the  nature  of  the  materials  which  are 
oxidized.  It  has  long  been  known  that  urea  excretion  is  abnor- 
mally high  in  fever,  and  this  led  to  the  inquiry  whether  the  rise 
was  merely  the  result  of  increased  body  temperature  or  was  due 
to  toxic  influences.  Thus,  Schleich^  finds  that  a  man  in  nitrogen 
equilibrium  is  affected  by  an  hour's  bath  in  water  between  40.5° 
and  41.5°  which  causes  his  temperature  to  reach  39.7°,  so  that  his 
nitrogen  metabolism  for  the  day  increases  18,  22,  and  37  per  cent. 
Other  authors  have  not  found  any  increase,  but  Linser  and 
Schmid^  explain  these  divergences  of  opinion  by  showing  that 
an  increase  of  body  temperature  to  39°  in  man  has  no  effect  on 
protein  metabolism,  but  that  above  this  there  is  always  an  in- 
creased destruction  of  protein.  They  therefore  conclude  that  in 
toxic  fevers  where  the  temperature  is  not  above  39°  any  increase 
of  protein  metabolism  must  be  due  to  the  toxic  processes  and  not 
to  the  hyperthermia. 

F.  Voit^  found  that  on  artificially  raising  the  temperature  of 
a  fasting  dog  to  40°  or  41°  for  a  period  of  twelve  hours,  there  was 
an  increase  in  nitrogen  elimination  of  37  per  cent,  above  the 
normal.  Warming  for  a  period  of  only  three  hours  had  slight 
efifect.  If,  however,  the  animal  were  fed  with  meat  and  fat, 
warming  increased  the  protein  metabolism  only  4  per  cent. 

'Schleich:    "Archiv  filr  ex.  Path,  und  Pharm.,"  1875,  Bd.  iv,  p.  90. 
^Linser  and  Schmid:  Loc.  cil. 

*Voit,  F.:  ".Sitzungsberichte  der  Gesellschaft  fur  Morphologic  und  Phys- 
iologic," 1895,  Heft  ii,  p.  120. 


314 


SCIENCE    OF   NUTRITION, 


If  the  animal  were  given  30  to  40  grams  of  cane  sugar,  no 
increased  metabolism  of  protein  followed  the  rise  in  temper- 
ature to  41°.  It  is  apparent  that  the  ingestion  of  protein  aiid 
carbohydrates  may  control  this  rise  in  protein  destruction  due 
to  a  febrile  temperature.  F.  Voit  explains  the  increase  in  pro- 
tein metabolism  in  hyperthermia  as  due  to  the  quick  combustion 
of  glycogen  and  the  consequent  impoverishment  of  the  tissues 
as  regards  carbohydrate  material.  Protein  or  carbohydrate 
ingesta  furnish  the  necessary  carbohydrate  and  prevent  the 
hyperthermal  rise  in  protein  metabolism.  The  destruction  of 
protein  due  to  toxic  processes  cannot  be  so  easily  controlled,  as 
will  be  seen  later. 

If  certain  portions  of  the  brain  be  punctured,  and  particu- 
larly the  region  of  the  corpora  striata,  a  high  fever  sets  in.  Here 
again  there  is  an  increased  output  of  carbon  dioxid  and  a  rise 
in  protein  metabolism.  This  phenomenon  has  been  recently 
investigated  by  Hirsch,  Miiller,  and  Rolly^  and  by  Rolly^  alone. 
They  find  that  after  the  "heat  puncture"  of  the  corpora  striata 
the  liver,  blood,  and  skin  become  warmer  than  the  muscles, 
although  normally  the  muscles  are  warmer  than  the  skin. 
They  find  that  the  heat  puncture  is  effective  even  in  curarized 
animals,  where  the  muscles  are  free  from  nerve  stimuli.  Roily 
finds,  however,  that  the  heat  puncture  is  ineffective  if  the 
liver  of  the  rabbit  has  been  previously  freed  from  glycogen  by 
strychnin  convulsions.  Under  these  circumstances  there  is  no 
rise  in  temperature  nor  concomitant  rise  in  protein  metabolism. 
The  inference  is  that  the  fever  in  question  is  due  to  nerve  im- 
pulses which  increase  the  metabolism  of  carbohydrate  in  the  liver. 
In  infectious  fever  there  is  little  glycogen  in  the  organism,  but 
that  the  fever  in  this  case  is  due  to  other  causes  than  the  rapid 
combustion  of  carbohydrates  was  shown  by  Roily,  who  infected 
a  rabbit,  which  had  been  freed  from  glycogen  as  above  described, 
with  a  culture  of  pneumococci  and  obtained  as  great  a  rise  in 

^Hirsch,  Miiller, and  Roily:  "Deutsches  Archiv  fiir  klin.  Med.,"  1903,  Bd. 
Ixxv,  p.  264. 

^ Roily:   Ibid.,  1903,  Bd.  Ixxviii,  p.  250. 


METABOLISM  IN  FEVER. 


315 


temperature  and  protein  metabolism  as  would  have  occurred 
had  the  tissues  of  the  rabbit  been  rich  in  carbohydrates.  The 
rise  in  temperature  after  puncture  of  the  corpora  striata  may  be 
termed  neurogenic  fever,  and  it  is  like  the  glycosuria  following 
Claude  Bernard's  puncture,  in  that  its  mechanism  is  no  more 
invoked  in  true  infectious  fever  than  are  the  nerve  centers  in 
diabetes  meUitus  (p.  272). 

If  the  extent  of  metabolism  in  infectious  fevers  be  inves- 
tigated and  compared  with  that  found  in  simple  hyperthermia, 
a  closely  analogous  state  of  affairs  is  discovered.  The  course 
taken  by  the  metabolism  in  toxic  fevers  is,  as  a  rule,  (i)  a  slight 
rise  in  protein  metabolism,  even  before  the  fever  sets  in;  (2) 
increased  metabolism  with  heat  retention  and  increased  protein 
destruction;  (3)  heat  production  and  heat  outgo  become  equal, 
with  the  body  at  a  higher  temperature  level.  These  factors  are 
illustrated  in  the  experiments  of  May'  on  fasting  rabbits  in- 
jected with  a  culture  of  erysipelas  of  the  pig.  The  results  of 
these  respiration  experiments  with  three  rabbits,  in  which  the 
normal,  transition,  and  fever  periods  were  investigated,  are 
given  below. 

METABOLISM  IN  FEVER  IN  RABBITS  (May). 


Body 
Temperature. 

Calories. 

Rabbit. 

Day 
OF  Fast, 

From  1   ^ 

Total.        Pro-     ;    f^°"^ 
tein.   j     ^^'• 

Remarks. 

E 

3 

4 

S 

3 
4 
5 
6 

I 

5 

39-2-39-S 
39.7-41.2 
41.2-40.7 

38.5-38.2 
38.2-38.6 
38.6-38.6 
38.7-40.1 

39.0-39.6 
39.6-39.2 
39.7-41.0 

61.9 
63.9 
73-3 

53-8 
54.0 
55-4 
61.2 

64.5 
64.2 
65.8 

18 

19 

27 

16.8 
18.5 
20.6 
27.9 

10.7 
10.4 
11.8 

44 
45 
46 

35-6 
34-8 
33-3 

53-8 
53-7 
54-0 

Normal. 

G 

Injection. 
Fever. 

Nonnal. 

H 

Injection. 
Fever. 

Normal. 

Injection. 

>May:   "Zeitschrift  fur  Biologic,"  1894,  Bd.  xxx,  p.  i. 


3l6  SCIENCE   OF   NUTRITION. 

The  above  table  shows  a  slight  increase  in  the  protein  me- 
tabolism on  the  day  of  infection.  It  also  shows  that  a  high 
fever  may  be  reached  by  the  end  of  the  twenty-four  hours  after 
the  injection  without  materially  altering  the  heat  production 
of  the  day.  It  demonstrates  that  on  the  day  of  continued  fever 
the  metabolism  increases,  and  this  at  the  expense  of  an  increased 
destruction  of  protein,  while  the  fat  consumption  remains  un- 
altered. A  calculation  shows  that  on  the  days  of  high  fever 
20  per  cent,  more  energy  was  produced  in  rabbit  E,  and  15  per 
cent,  more  in  rabbit  G,  than  on  normal  days.  Since  Traube's 
writings  on  the  subject  were  published,  the  cause  of  fever  has 
been  attributed,  not  to  great  heat  production,  but  to  a  disturbance 
in  the  mechanism  for  the  regulation  of  heat  loss.  On  recalling 
the  fact  that  the  metabolism  of  a  fasting  dog  may  be  raised  from 
100  calories  in  starvation  to  189  calories  after  giving  meat  (p. 
153),  without  any  change  of  body  temperature,  it  becomes 
evident  that  the  rise  in  metabolism  in  fever  is  too  insignificant  to 
be  the  cause  of  the  rise  in  temperature.  In  fact,  as  has  been 
already  set  forth,  the  rise  in  body  temperature  from  failure  of  the 
physical  regulation  may  of  itself  explain  the  increase  in  heat  pro- 
duction. Thus  a  calculation  made  in  the  case  of  rabbit  E 
shows  that  the  carbon  dioxid  elimination  is  increased  6.6  per 
cent,  for  each  degree  of  rise  in  temperature,  which  corresponds 
to  Pfliiger's  experiments,  before  mentioned,  in  which  artificially 
warmed  normal  rabbits  excreted  6.8  per  cent,  more  carbon 
dioxid  for  each  degree  of  rise  in  temperature. 

Staehelin^  infected  a  dog  by  inoculating  him  with  1.5  cc.  of 
dog's  blood  containing  surra  trypanosomes  which  are  active 
flagellate  parasites.  Fever  set  in  on  the  sixth  day  after  the 
inoculation  and  the  dog  died  on  the  twenty-fifth  day.  The 
metabolism  due  to  the  infection  rose  to  88.9  calories  per  kilogram 
on  the  tenth  day  after  inoculation  as  against  a  normal  of  59.8, 
an  increase  of  48  per  cent.  On  this  febrile  day  26  per  cent,  of 
the  total  energy  was  yielded  by  protein;  the  body  lost  2.8  grams 

^Staehelin:    "Archiv  fur  Hygiene,"  1904,  Bd.  1,  p.  77. 


METABOLISM   IN    FEVER. 


317 


of  nitrogen  which  indicated  a  high  toxic  waste.  However,  all 
the  increase  in  the  heat  production  did  not  come  from  increased 
protein  metabohsm  as  in  the  case  of  May's  rabbits,  but  the  fat 
destruction  was  also  increased,  and  Staehelin  speaks  of  a  toxic 
waste  of  fat.  He  also  remarks  that  the  dog  remained  perfectly- 
quiet  during  the  period  of  the  experiment,  but  he  does  not  say 
whether  thermal  influences  which  could  result  in  chill  were 
completely  excluded.  However,  he  came  to  the  conclusion  that 
in  this  fever  caused  by  trypanosomes  the  metabolism  was  higher 
than  could  be  explained  by  the  over-warming  of  the  body, 
an  explanation  which  sufficed  in  the  case  of  May's  rabbits. 

During  the  last  days  of  life  the  body  temperature  fell  and 
with  it  the  amount  of  the  metabolism.  The  following  table 
gives  a  partial  record  of  the  daily  metabolism  in  this  dog: 

METABOLISM  IN  FEVER  INDUCED  BY  SURRA  TRYPANOSOMES. 


Period. 


I.  Normal  (average) . . 
II.  Inoculation        and 

prodromal 

III.  ist  of  fever 


Q2 


z 


9 
10 


IV.  2d  of  fever  (aver- 
age)  11-17 

V.  3d   of  fever  (aver- 
age)  

VI.  Final  period  (aver- 
age)  


21-24 


5-67 

5-67 
5-67 
5-67 
5-67 
5-67 

4-37 

3-34 


+  0.15 

—  0.18 

—  0.40 

—  0.46 
— 1.06 

—  2.80 

2.50 
2.52 

—  4-63 


585 

58s 
585 
585 
585 
585 

451 
348 


OS 


510.0 

469-3 
521.4 

556.9 
675.2 

729-3 
665.2 
665.0 
521.0 


^3 


59-8 

58.3 
63-9 
68.2 
81.6 
88.9 

83-7 
74.0 
62.0 


U6 


1027 

9S2 
1081 

1154 
1388 

1507 
1404 
1218 
907 


Body 
Temp. 


Max. 


39-4 
39-5 
39-6 
40.1 
39-2 


40.4 
38-8 


Min. 


38.3 
38.3 
37-7 
39-6 
37-9 


38-S 
35-5 


Long  before  May's  experiments.  Wood'  had  found  an 
average  increase  of  23  per  cent,  (calculated  by  Welch)  in  the 
heat  production  of  fasting  dogs  after  inducing  fever;  and  he 

'  Wood:  "  Fever,"  Philadelphia,  1880. 


3l8  SCIENCE   OF  NUTRITION. 

also  found  that  mere  ingestion  of  food  by  a  normal  dog  would 
cause  a  greater  heat  production  than  fever  itself. 

Traube  attributed  the  cause  of  fever  to  a  cramp-like  con- 
striction of  the  peripheral  arterioles  which  prevented  the  proper 
distribution  of  blood  at  the  surface,  and  therefore  hindered  the 
normal  cooling  of  the  body. 

The  effect  of  a  cold  bath  upon  a  vigorous  man  is  to  constrict 
the  peripheral  blood-vessels  and  to  increase  the  heat  production. 
The  body  temperature,  instead  of  falling,  may  rise  for  eight  or 
ten  minutes  and  then  sink.^  If  the  individual  pass  from  the  bath 
during  the  earlier  minutes  the  hot  blood  comes  to  the  surface 
to  be  cooled,  and  the  body  glows  with  a  red  color,  the  so-called 
"reaction."  This  experiment  shows  that  there  are  factors 
invoked  during  the  first  few  minutes  which  prevent  the  dis- 
charge of  the  heat  produced.  One  factor  must  be  a  general 
constriction  of  the  peripheral  arteries,  causing  the  blood  to 
remain  in  the  heat-producing  inner  organs  of  the  body.  In 
this  experiment,  therefore,  cooling  of  the  organism  is  prevented 
by  the  mechanism  of  physical  regulation  above  described,  and 
the  mechanism  of  chemical  regulation  which  refiexly  increases 
heat  production. 

To  combat  a  rise  in  temperature,  however,  the  only  means 
available  is  the  physical  regulation, — i.  e.,  the  change  in  the 
distribution  of  the  blood  and  the  production  of  sweat.  If  these 
avenues  of  heat  loss  be  diminished  or  shut  off,  heat  accumulates 
within  the  body  and  temperature  rises.  Why  an  increase  in 
heat  production  of  89  per  cent,  may  not  cause  a  rise  in  tempera- 
ture in  a  normal  animal  has  already  been  explained;  whereas, 
a  high  fever  may  be  accompanied  by  an  increased  metabolism 
of  only  15  per  cent.  The  cause  of  the  fever  must  therefore  be  a 
diminution  in  the  ability  to  discharge  the  heat  produced. 

In  further  support  of  this.  Senator  has  shown  that  the  fever 
following  pus  injections  in  a  dog  begins  with  a  retention  of  heat 
within  his  body.     Nebelthau^  found  in  a  rabbit  that  during  the 

^Lefevre,  J.:   "Comptes  rendus  soc.  biol.,"  1894,  T.  xlvi,  p.  604. 
^Nebelthau:    "Zeitschrift  fiir  Biologic,"  1895,  Bd.  xxxi,  p.  353. 


METABOLISM   IN   FEVER.  319 

first  twelve  hours  of  infection  in  which  the  temperature  rose  from 
38.6°  to  40.1°,  the  discharge  of  heat  was  but  96.3  per  cent,  of 
that  of  the  previous  period.  Assuming  the  heat  produc- 
tion to  have  been  the  same  in  these  two  periods  (as  was  actu- 
ally the  case  in  the  rabbits  of  May),  then  the  retention  of  heat 
would  account  for  the  pathological  increase  in  temperature.  At 
a  later  stage  the  discharge  of  heat  rose  to  equalize  its  production 
at  the  higher  temperature. 

Nebelthau  has  sho\\'n  a  fall  in  temperature  and  heat  produc- 
tion in  a  rabbit  whose  cord  was  divided  between  the  sixth  and 
seventh  cervical  vertebrae,  and  has  also  demonstrated  that  under 
these  circumstances  infection  with  erysipelas  of  the  pig  had  no 
influence  on  temperature  or  heat  production.  The  inference  is 
that  the  febrile  toxins  act  through  the  higher  vasomoter  centers, 
whose  regulatory  control  is  lost  in  the  above  experiment. 

A  kindred  interpretation  may  be  placed  on  the  experiments 
of  ^Mendelson,^  who  was  unable  to  produce  fever  through  pus 
injections  when  the  dog  was  under  the  influence  of  chloral  or 
morphin,  although  such  treatment  in  a  normal  animal  caused 
a  rise  in  temperature  of  from  36.3°  to  39.9°  in  forty-five  minutes. 
Mendelson  also  finds  a  constant  constriction  of  the  renal  blood- 
vessels in  fever. 

Further  experimentation  convinced  Sawadowsky^  that  fever 
cannot  be  produced  after  the  mid-brain  has  been  severed  from  the 
medulla,  whereas  if  the  mid-brain  be  left  intact,  but  the  cere- 
brum be  sectioned  from  it,  fever  may  be  induced  in  the  ordinary 
course.  The  toxic  substance  must  therefore  act  on  nerve-cells 
in  the  mid-brain,  which  in  turn  stimulate  the  medullary  centers. 

At  times  during  high  fever  the  skin  may  be  red  and  the 
peripheral  blood-vessels  distended.  Although  there  is  no 
sufficient  explanation  for  the  continuance  of  fever  when  the 
radiation  and  conduction  of  heat  from  the  surface  of  the  body  are 

*  Mendelson:   "Virchow's  Archiv,"  1885,  Bd.  c,  p.  274. 
*Sawadowsky:    "  Centralblatt  fur  medizinische  Wissenschaft,"   1888,  Bd. 
xxvi,  p.  161. 


320 


SCIENCE   OF  NUTRITION. 


thus  increased,  KrehP  suggests  that  the  quantity  of  blood  flowing 
through  the  vessels  at  the  time  may  be  inadequate  to  reduce 
the  body's  temperature. 

The  second  means  of  physical  regulation  of  the  body  tem- 
perature is  through  the  evaporation  of  water  from  both  the  lungs 
and  the  sweat  glands.  It  might  be  surmised  that  the  activity 
of  this  mechanism  was  reduced  in  fever.  Nebelthau^  has  shown 
that  the  heat  lost  by  evaporation  of  water,  and  by  radiation  and 
conduction,  bear  exactly  the  same  ratio  to  each  other  in  normal 
and  in  fever-infected  rabbits.  Since  Rubner  (p.  98)  has  proved 
that  the  elimination  of  water  in  normal  animals  greatly  increases 
at  high  temperatures,  the  mere  maintenance  of  the  usual  water 
evaporation  during  fever  would  of  itself  be  abnormal. 

No  complete  metabolism  experiment  on  a  man  suffering 
from  high  fever  has  ever  been  made,  and  here  is  an  opportunity 
for  some  one  to  perform  a  rare  service.  By  no  means  the  least 
interesting  phase  of  such  an  experiment  would  be  the  course  of 
water  elimination  from  the  skin. 

Lang^  has  shown  that  the  elimination  of  sweat  is  reduced 
during  the  rise  of  temperature  in  man,  but  at  the  height  of  fever 
is  the  same  as  the  normal,  while  there  is  some  increased  evapora- 
tion from  the  lungs. 

Recent  experiments  by  Schwenkenbecker  and  Inagaki* 
show  that  the  "insensible  perspiration"  in  fever  is  as  great  as 
in  health,  and  that  although  the  urine  may  decrease  in  quantity 
there  is  no  actual  accumulation  of  water  in  the  body  as  was  be- 
lieved by  von  Leyden  (see  p.  331). 

Lang^  has  also  shown  that  the  secretion  of  sweat  is  increased 
50  per  cent,  after  the  ingestion  of  food  as  against  an  increase 
of  70  per  cent,  in  the  normal  individual. 

^Krehl:   " Pathologische  Physiologie,"  1904,  p.  453. 
^Nebelthau:  Loc.  cit. 

^Lang:   "Archiv  fiir  klinische  Medizin,"  1903,  Bd.  Ixxix,  p.  343. 
*  Schwenkenbecker  and    Inagaki:    "Archiv  fiir  ex.   Path,   und    Pharm.," 
1906,  Bd.  liv,  p.  168. 
^Lang:  Loc.  cit. 


METABOLISM  IN  FEVER.  32I 

In  intermittent  fever  profuse  perspiration  is  certainly  an 
important  factor  in  the  reduction  of  temperature  at  the  end  of 
the  febrile  stage. 

It  may  be  concluded,  as  KrehP  emphatically  states,  that 
insufficiency  of  water  evaporation  plays  a  not  unimportant  role 
in  the  febrile  rise  in  temperature.  The  body  might  be  cooled 
were  the  sweat  glands  freely  active. 

The  production  of  heat  in  fever  may  be  greatly  increased 
during  a  chill,  and  a  rapid  rise  in  temperature  may  follow. 
This  was  sho^\^l  by  Liebermeister^  in  a  case  of  malaria.  The 
temperature  rose  from  36.9°  in  the  first  half  hour  to  39.5°  at  the 
end  of  another  hour,  while  the  carbon  dioxid  expired  rose  from 
13.85  grams  to  34.20  grams  per  half  hour.  This  was  a  case  of 
chill  with  shivering.  This  increased  metabolism  is  due  to  the 
mechanism  of  chemical  regulation.  The  blood  is  driven  from 
the  skin  by  vaso-constriction,  those  end-organs  of  the  skin  which 
are  sensitive  to  cold  are  strongly  stimulated,  with  the  result  that 
there  is  a  reflex  increase  of  heat  production.  That  this  is  true 
is  showTi  by  the  fact  that  if  the  cold  stimulation  be  removed  by 
supplying  a  warm  environment,  the  attending  phenomena  pass 
off  (Krehl).' 

Any  muscular  exercise,  such  as  sitting  up,  increases  metab- 
olism, and  may  under  some  circumstances  cause  a  rise  in  temper- 
ature in  fever.  (Compare  with  effect  of  tetanus,  p.  270.)  The 
diurnal  variation  of  temperature  is  similar  in  character  to  that 
of  health,  but  its  fluctuations  are  much  more  extreme,  on  account 
of  the  increased  excitability  of  the  vasomotor  control  of  the  dis- 
charge of  heat.  The  parallelism  between  the  amount  of  the 
metabolism  and  the  height  of  the  temperature  during  the  day 
is  shown  in  Fig.  10,  taken  from  Ricthus.* 

It  is  apparent  that  cold  and  muscular  work  increase  metab- 

*  Krehl:   "  Clinical  Pathology,"  1907,  p.  403- 

'Liebermeister:  "Deutsches  Archlv  fiir  klinisches  Medizin,"  1871,  Bd. 
viii,  p.  15,3. 

*  Krchl:   " Pathologische  Physiologic,"  1904,  p.  452. 

*Riethus:    "Archiv  fur  ex.  Path,  und  Pharm.,"  1900,  Bd.  xliv,  p.  239. 


322 


SCIENCE   OF  NUTRITION. 


olism  and  temperature  in  fever,  and  it  may  be  also  surmised 
that  large  protein  ingestion,  which  by  its  specific  dynamic 
action  increases  heat   production,   will  likewise   increase   the 


6 
S 

3 
Z 

1 

ho 

38 
37 
S6 

^ 

A 

A 

/ 

- 

e.oz 

V 

N/" 

-^ 

/ 
/ 

/^' 

/ 

^V^ 

-^ 

^ 
^ 

5^ 

Mi 

SI 

^1 

? 

'-^J 

1 

1 

1 

<>> 

^ 

S=^ 
^ 

Fig.  lo. — Case  of  abdominal  typhoid  (Riethus).  The  figures  i  to  6  on  the 
left  represent  the  amount  in  c.c.  of  CO2  and  Oj  of  respiration  per  kilogram  and 
minute.  The  measurements  were  all  made  during  fasting.  The  O^  curve 
may  be  considered  as  nearly  proportional  to  the  heat  production  (p.  2,1). 


METABOLISM  IN  FEVER. 


323 


body's  temperature  at  a  time  when  heat  discharge  is  difficult 
(p.  163). 

May^  summarizes  the  conditions  of  metabolism  in  fever  in 
the  following  statement:  "There  is  an  increased  protein  metab- 
olism but  no  increased  fat  metabolism,  except  such  as  may 
incidentally  result  from  dyspnea,  chill,  or  muscular  activity." 

Infectious  fevers  are  characterized  by  a  toxic  destruction  of 
body  protein.  Sometimes,  as  in  the  earlier  stages  of  tuber- 
culosis, this  tissue  destruction  may  be  present  in  the  absence  of 
fever  itself.  Such  a  toxic  action  on  body  protein  is  also  ob- 
served in  cancerous  cases,  as  was  described  by  Fr.  Miiller.^ 
Miiller  writes:  "In  the  seven  cases  (of  carcinoma)  cited,  the 
nitrogen  excretion  was  larger  than  the  nitrogen  ingestion  and 
consequently  the  body  lost  protein.  In  two  cases  the  protein 
loss  was  no  greater  than  in  healthy  individuals  with  similar 
insufficient  nourishment.  In  all  the  other  cases  the  protein 
metabolism  was  decidedly  above  that  of  healthy  men  under  the 
same  conditions.  Even  an  ample  dietary  was  not  able  to  estab- 
lish nitrogen  equilibrium.  As  more  food  was  given  the  nitrogen 
elimination  rose  higher  and  higher,  but  the  point  of  nitrogen 
equilibrium  seemed  unattainable."  Miiller  compared  the 
cachexia  of  carcinoma  with  that  found  in  febrile  processes  and 
believed  them  to  be  analogous. 

As  regards  tuberculosis  Ma/  writes:  "Larger  quantities  of 
the  toxins  produce,  with  certain  exceptions,  a  direct  injury  to 
the  cell  protoplasm.  They  are  strongly  toxic.  The  quantity 
of  protein  destruction  attributable  to  this  cause  is  not  very  large 
and  becomes  of  importance  only  when  continued  for  a  long 
period  of  time  and  whgre  there  is  no  compensatory  regeneration. 
It  appears  that  the  power  to  regenerate  on  the  part  of  these  cells 
which  are  destroyed  by  toxins  is  greatly  reduced  and  in  severe 
cases  entirely  lost." 

'May:   Ott's  "Chemische  Pathologic  der  Tuberculosc,"  1903,  p.  355. 
*  MuUer,  F.:   "Zeitschrift  fur  klinischc  Mcdizin,"  1889,  lid.  xvi,  p.  496. 
'May:    Ott's  "Chemische  Pathologic  dcr  Tuberculosc,"  1903,  p.  335. 


324  SCIENCE   OF  NUTRITION. 

Other  fevers  show  a  high  toxic  destruction  of  protein.  F. 
Miiller^  reports  a  daily  loss  of  10.8  grams  of  nitrogen  (equal  to 
318  grams  of  muscle)  by  a  typhoid  patient  during  eight  days  of 
fever.  During  fever  in  croupous  pneumonia,  the  protein 
metabolism  is  much  higher  than  normal.  After  the  crisis  there 
is  still  a  large  excretion  of  nitrogen  in  the  urine  which  continues 
until  the  croupous  exudate  has  been  decomposed  by  autolysis, 
absorbed  by  the  blood,  and  metabolized  in  the  body  (epicritical 
nitrogen  elimination).  In  acute  pneumonic  phthisis  (galloping 
consumption),  with  its  caseous  transformation  of  lung  tissue, 
there  is  a  very  high  waste  of  tissue  protein.  F.  Miiller^  has 
shown  that  while  the  croupous  exudate  readily  undergoes  auto- 
lysis at  a  temperature  of  40°,  with  the  production  of  deutero- 
albumoses,  lysin,  leucin,  tyrosin,  etc.,  the  caseous  mass  does 
not  undergo  autolysis  although  it  permits  free  diffusion  of  solu- 
ble material,  such  as  phosphates.  Hence,  although  the  protein 
of  the  cheesy  mass  is  insoluble  in  the  organism,  the  soluble 
toxins  may  be  absorbed  from  the  diseased  part,  and  be  the 
causative  agent  of  the  rapid  destruction  of  body  protein  in  gal- 
loping consumption. 

The  above  analysis  of  metabolism  in  fever  shows  that  the 
small  increase  in  total  metabolism  is  associated  with  increases 
in  protein  metabolism  due  (i)  to  the  high  temperature,  and  (2) 
to  the  virulence  with  which  toxins  attack  the  body  tissue.  It 
has  been  shown  that  carbohydrate  ingestion  may  reduce  the 
protein  destruction  due  to  the  overheating,  and  that  toxic  de- 
struction may  or  may  not  be  compensated  for  by  regenerative 
processes.  Upon  this  general  knowledge  it  is  possible  to  con- 
struct a  dietary  schedule  for  the  patient. 

In  all  fevers  the  septic  products  act  upon  the  hunger  centers 
in  the  brain,  and  appetite  is  wanting.  This  is  evidenced 
throughout  the  course  of  tuberculosis,  for  example,  and  tends  in 

^Miiller,  F.:    "  Centralblatt  fiir  klinische  Medizin,"  1884,  No.  xxxvi. 
^Muller,   F.:    "  Verhandlungen  des  20    Congresses  fiir  innere   Medizin," 
1902,  p.  192. 


METABOLISM   IN   FEVER. 


325 


this  case  to  weaken  the  body's  resistance  through  undernutri- 
tion.    Forced  feeding  is  therefore  resorted  to. 

The  experiments  of  von  Hosslin^  strongly  affirmed  the  bene- 
ficence of  a  liberal  diet  in  ordinary  fevers.  He  writes:  "The 
results  show  that  febrile  patients,  or  at  least  those  who  do  not 
run  temperatures  above  40°  to  40.5°,  can  digest  and  absorb 
the  total  amount  of  protein,  fat,  and  carbohydrates  which  can 
be  given  them  with  their  diminished  appetite,  provided  the  food 
is  administered  in  a  proper  form.  Temperature  and  metabolism 
are  only  slightly  increased  thereby." 

A  milk  diet  is  the  usual  course  prescribed  in  fevers.  Since 
milk  is  the  proper  diet  for  a  rapidly  growing  calf,  its  protein  con- 
tent is  extremely  high.  The  relative  quantity  of  this  ingredient 
may  be  reduced  by  modifying  the  milk  through  the  addition 
of  milk  sugar  or  cream.  In  this  way  von  Leyden  and  Klem- 
perer^  have  added  5  per  cent.,  then  7.5,  and  finally  10  per  cent, 
of  milk  sugar  to  whole  milk.  The  last  named  quantity  raises 
the  calorific  value  by  410  calories  per  liter,  and  makes  a  milk 
containing  1050  calories  per  liter.  Two  liters  of  such  milk 
would  be  nearly  or  quite  sufficient  to  cover  the  requirement  of 
an  individual  confined  to  his  bed.  A  milk  so  prepared  may  be 
given  to  most  patients  without  producing  diarrhea  or  indigestion. 
The  taste  is  perfectly  agreeable  to  the  patient.  In  this  way 
carbohydrates,  which  are  highly  desirable  in  the  febrile  condition, 
can  be  properly  administered.  Von  Leyden  and  Klemperer 
have  also  found  that  an  addition  of  cream  to  milk,  so  that  its 
value  is  increased  by  2.5  per  cent,  of  fat,  or  225  calories  per 
liter,  is  favorably  received  by  the  patient.  Such  a  milk  diet  may 
be  fortified  by  the  addition  of  brandy,  whiskey,  or  sherry.  This 
increases  the  calorific  value  of  the  milk,  but  more  particularly 
gives  it  taste,  and  both  through  the  awakening  of  the  sense  of 
appetite  and  through  direct  action  upon  the  neuro-secretory 

'Von  Hosslin':   "Virchow's  Archiv,"  1882,  Bd.  Ixxxix,  p.  317. 
^Von  Leyden  and  Klemperer:   Von  Leyden's  "Handbuch  der  Ernahrungs- 
therapie,"  1904,  Bd.  ii,  p.  345. 


326 


SCIENCE   OF  NUTRITION. 


apparatus  of  the  digestive  tract,  favorably  influences  the  diges- 
tion of  the  food. 

It  seems  strange  that  in  this  country  where  so  much  attention 
has  been  paid  to  the  modification  of  infant  food,  the  preparation 
of  suitable  diet  in  fever  should  have  received  such  scant  attention. 
It  may  well  be  that  investigation  will  show  that  dilution  of 
milk  and  its  fortification  by  ingredients  other  than  protein 
may  be  as  advantageously  practised  in  fever  cases  as  in  infant 
nutrition. 

The  discussion  now  turns  from  these  theoretical  considera- 
tions to  the  actual  results  of  nutritive  investigations  in  fever  as 
presented  by  von  Leyden  and  Klemperer. 

The  following  table  represents  a  case  of  a  typhoid  fever 
patient  to  whom  milk  fortified  with  meat  powder  was  given, 
thereby  producing  a  high  protein  diet.  The  quantity  of  the 
individual  nutrients,  the  calorific  value  of  the  diet,  and  the 
nitrogen  in  the  urine  and  feces  were  determined.  The  daily 
loss  of  body  nitrogen  was  calculated.  The  results  were  as 
follows : 


METABOLISM  IN  TYPHOID;  DIET  HIGH  IN  PROTEIN. 

Food. 

Excreta. 

High- 

Loss 

est 

>,  . 

OF 

Temp. 

Amount 

Calo- 

N. 

Fat. 

-gs 

Urine 

Feces 

Total 

Body 

N. 

in  Grams. 

ries. 

6'^ 

N. 

N. 

N. 

39-6 

600  milk. 

408 

3-2 

21 

27 

15.76 

0.42 

16.18 

12.98 

39.8 

1000  milk. 

680 

5.36 

35 

45 

18.96 

0.42 

19.38 

14.02 

40.2 

900  milk. 

20  meat-powder. 

686 

7.67 

31 

40 

17.88 

0.42 

18.30 

10.63 

39-7 

1200  milk, 
so  meat-powder. 

1002 

13-61 

42 

54 

21.56 

1.75 

23.31 

9.70 

39.9 

1500  milk, 
100  meat-powder. 

1392 

22.45 

52 

67 

28.7 

1.75 

30.45 

8.00 

40-3 

1200  milk, 
50  meat-powder. 

11S8 

20.86 

42 

54 

27-9 

1-75 

29.65 

8.79 

40-3 

1500  milk, 
so  meat-powder. 

1206 

IS. 2 

52 

67 

21.7 

1.92 

23-92 

8.42 

39-8 

2000  milk, 

so  meat-powder. 

1546 

17.8s 

70 

90 

22.9 

1.92 

24.82 

6.97 

40.2 

2000  milk, 
100  meat-powder. 

1732 

25.1 

70 

90 

29.6 

1.92 

31-52 

6.42 

39-9 

2000  milk, 

so  meat-powder. 

1546 

17.8s 

70 

90 

20.85 

2.13 

22.98 

5-13 

39-8 

1200  milk, 
50  meat-powder. 

1002 

13-61 

42 

54 

19.76 

2.13 

21.89 

8.28 

39-9 

1500  milk, 

1020 

8.0 

52 

67 

15-86 

2.13 

18.02 

10.02 

METABOLISM   IN   FEVER. 


327 


It  will  be  noted  that  there  was  a  large  loss  of  body  nitrogen 
on  every  day  of  the  experiment.  Even  when  the  diet  con- 
tained 25.1  grams  of  nitrogen,  the  excreta  of  the  day  contained 
31.5  grams,  indicating  a  loss  of  6.4  grams  from  the  body.  The 
days  of  the  smallest  loss  of  tissue  nitrogen  were  those  on  which 
the  largest  quantity  (90  grams)  of  carbohydrates  was  given. 
Also  a  diet  containing  17.85  grams  of  nitrogen  seems  to  protect 
the  protein  waste  about  as  well  as  one  with  25.1  grams  of  nitrogen 
when  both  diets  contain  equal  quantities  of  carbohydrates 
and  fat. 

Von  Leyden  and  Klemperer  regard  the  above  experiment 
as  indicating  the  advantage  of  a  large  protein  ingestion  in  pre- 
venting tissue  waste.  But  deficient  calorific  value  and  lack  of 
carbohydrates  may  be  accountable  for  the  increased  waste 
on  the  lower  protein  diets.  It  must  also  be  remembered  that 
protein  itself  yields  carbohydrate  in  metabolism.  That  carbo- 
hydrates of  themselves  cannot  prevent  the  toxic  waste  of  protein 
tissue  is  apparently  illustrated  in  another  experiment  given  by 
the  same  authors.  The  case  was  again  one  of  typhoid,  and  carbo- 
hydrates were  given  in  large  quantity: 


METABOLISM  IN  TYPHOID;  DIET  HIGH  IN 

CARBOHYDRATE. 

High- 

Food. 

Excreta. 

est 

TZMP. 

Quantity  in 
Grams. 

Calo- 
ries. 

Nin 
Grams. 

Fat  in 
Grams. 

Garb. 

in 
Grams. 

Urine 

N  in 
Grams. 

Feces 

Nin 

Grams. 

Loss  of 
Body 
Nin 

Grams. 

39.8        2808  milk. 

3020 

14.9 

98 

386 

20. 1 

i-S 

6.7 

400  lactose, 

60  Klucose, 

i  liter  sherry. 

39.7 

2768  milk, 
200  lactose, 
133  Klucose, 
4  liter  sherry. 

3295 

14.6 

96 

457 

19.7 

i-S 

6.6 

38.8 

2460  milk, 
300  lactose, 
1  liter  sherry. 

2952 

I3-0 

86 

4H 

23-7 

1-3 

12.0 

40.2 

2366  milk, 
300  lactose, 
1  liter  sherry. 

2892 

12-5 

83 

406 

233 

1.2 

12.0 

39.6 

2430  milk, 
109  lactose, 
i  liter  sherry. 

2522 

12.8 

8S 

310 

237 

1-3 

12.2 

38.8 

2080  milk, 
200  Klucose, 
f  liter  sherry. 

2420 

II. I 

80 

303 

21.8 

I.I 

1 1.8 

39a 

1870  milk, 
200  Klucose, 
1  liter  sherry- 

2141 

9.9 

6S 

344 

19.4 

I.O 

OS 

328  SCIENCE    OF   NUTRITION, 

In  this  case  it  is  apparently  shown  that  a  moderate  amount  of 
protein,  combined  with  a  large  quantity  of  fat  and  carbohydrates 
of  large  energy  content,  does  not  in  any  way  prevent  the  con- 
stant waste  of  body  tissue  in  typhoid  fever.  Since  it  has  been 
demonstrated  that  carbohydrates  prevent  tissue  destruction  due 
to  hyperthermia,  it  must  be  assumed  that  the  nitrogen  waste  is 
here  due  to  toxic  destruction  of  the  cells. 

May,  from  his  work  upon  fasting  rabbits  already  alluded  to, 
concluded  that  the  increased  protein  metabolism  in  fever  was 
in  large  measure  due  to  the  absence  of  available  carbohydrate, 
and  not  primarily  to  a  toxic  waste  of  tissue.  Thus  in  one  rabbit 
he  was  able  to  diminish  the  nitrogen  elimination  during  fever 
from  2.43  grams  to  1.29  grams  by  giving  30  grams  of  dextrose,  a 
reduction  of  47  per  cent. 

The  efficiency  of  a  carbohydrate  diet  in  typhoid  fever  has  been 
splendidly  demonstrated  by  Shaffer,^  who  has  shown  that  the 
ingestion  of  large  amounts  of  carbohydrate  in  a  low  protein 
diet  may  completely  or  almost  completely  maintain  the  patient 
in  nitrogen  equilibrium  throughout  the  disease.  The  diet 
consisted  of  milk,  milk  sugar,  diluted  cream,  eggs  and  sometimes 
arrowroot  starch.  Shaffer  writes:  ''It  was  only  when  we  gave 
60,  70,  or  even  80  calories  per  kilogram  of  bodyweight — ^between 
3000  and  4000  calories — that  the  greatest  sparing  was  observed." 

Dr.  Shaffer  has  kindly  allowed  the  use  of  heretofore  unpub- 
lished reports  on  two  individuals  suffering  from  typhoid  (see 
table  on  p.  329). 

From  this  it  may  be  concluded  that  nitrogen  equilibrium 
may  be  very  nearly  maintained  throughout  the  course  of  typhoid 
fever  on  a  diet  containing  12  to  15  grams  of  nitrogen,  provided 
an  excess  of  carbohydrate  beyond  the  requirement  of  the  or- 
ganism be  also  administered.  Very  likely  under  these  circum- 
stances the  fat  in  the  diet  is  without  influence,  except  that  it  is 
retained  in  the  organism.     As  to  whether  the  presence  of  carbo- 

^ Shaffer:  "Journal  of  the  American  Medical  Association,"  1908,  vol.  li, 
p.  974. 


METABOLISM   IN   FEVER. 


329 


hydrates  prevents  the  toxic  waste  of  body  protein,  or  provides 
conditions  for  a  compensatory  regeneration,  Dr.  Shaffer  is  not 
wiUing  to  express  an  opinion. 


INFLUENCE    OF    CARBOHYDRATES    ON    METABOLISAI 
PHOID  FEVER. 
SUBJECT  I. . 


IN    TY- 


Period. 


02 


OS 


I. 
II. 
III. 
IV. 
V. 
VI. 


Range  of  Maxi- 
mum Temp. 
During  Period. 


104  -103.2°  F. 
103.6-102.8°  F. 
103.8-103.4°  F. 
104.8-101.4°  F. 
100.8-  99.4°  F. 
Normal. 


q  Q 
d  o 
<  o 
On, 


4280 
5200 
2750 
5340 
4990 
2430 


Calories 
PER  Kg. 


From 
Total.  1  carbo- 
hydrates 


72 
85 
45 
89 

83 
41 


13-9 
15.0 
15.0 

14-5 
13.8 

13-5 


;z;h 


—  0.9 

—  0.2 

-8.5 

—  2.8 
-f   1.2 

—  0-3 


SUBJECT  II. 


I. 

II. 

III. 

IV. 

V. 


104.4-102.6°  F. 
102.8-100.6°  F. 

1920 
4290 

31 
70 

Normal. 
102.8-  99.6°  F. 

1930 
4800 

32 
78 

Relapse. 

Normal  convales- 
cence. 

2460 

39 

7.8 

47- 
8. 

SO- 


12.6 
12.6 
12.7 
14.1 

14.6 


— ii-S 
■ —  I.I 
-3-8 
+   3-6 


+   1.8 


♦  Average  for  last  three  days  of  diet. 

It  is  apparent  that  a  large  ingestion  of  protein  is  unnecessary, 
in  typhoid  at  least,  and  it  should  be  avoided  on  account  of  its 
extra  heat-producing  power-its  specific  dynamic  action. 

An  illustration  of  the  course  of  nitrogen  metabolism  m  a 
different  fever-namely,  pneumonia-may  also  be  taken  from 
von  Leyden  and  Klemperer.     The  details  are  given  on  p.  330. 

In  this  case  it  is  apparently  demonstrated  that  nitrogen 
equilibrium  cannot  be  obtained  during  high  fever,  and  also 
that  the  loss  of  body  nitrogen  does  not  cease  at  the  crisis,  bu 
rather  continues  on  account  of  the  epicritical  elimination  of 
nitrogen  derived  from  the  protein  of  the  croupous  exudate. 
During  the  time  of  this  epicritical  elimination  the  body  appears 


330 


SCIENCE   OF  NUTRITION. 


unable  to  add  new  protein  to  itself.  About  four  days  after  the 
crisis,  true  convalescence  begins  with  the  upbuilding  of  new  pro- 
tein tissue. 


METABOLISM  IN  PNEUMONIA. 


Food. 

Excreta. 

Temp,  on 

Successive 

Days. 

Quantity 
in  Grams. 

1 

N. 

Fat. 

0  «J 

Urine 

N. 

24.7 
22.8 

21.7 
21.9 
18.S 

18.7 

Feces 

N. 

Total 

N. 

Loss  OP 
Body 

N. 

40.8  (highest). 

40.9  (highest). 

41.2  at  12  M. 
36.8  at  7  p.  M. 

37.3  (highest). 

36.8  (highest). 
36.8  (highest). 

2000  milk. 
2000  milk, 

ISO  cream, 

100  lactose. 
2000  milk, 

ISO  lactose. 
2000  milk, 

200  cream. 
2000  milk, 

200  cream, 
2  eggs. 
2000  milk, 

300  cream, 
4  eggs. 

1360 
1980 

I97S 
1612 

1752 

2018 

10.6 
11.4 

10.6 
II. 7 
13-7 

17-3 

70 
8S 

70 

90 

100 

120 

90 
197 

240 
99 
99 

104 

0.9 
0.9 

0.9 
I.I 
I.I 

I.I 

25-6 
23-7 

22.6 
23-0 
19.6 

19.8 

I5-0 
12.3 

12.0 

11-3 

5-9 

2.S 

On  autopsy  of  patients  who  have  died  of  fevers,  parenchy- 
matous and  fatty  degenerations  of  the  organs  have  been  found. 
These  changes  have  been  ascribed  to  overheating  of  the  cells. 

Litten^  warmed  guinea-pigs  artificially  and  noted  fatty  but 
no  parenchymatous  degeneration  of  the  tissues.  The  space  in 
which  the  animals  were  kept  was,  however,  insufficiently  ven- 
tilated, and  the  fatty  change  might  have  been  caused  by  dyspnea, 
as  results  in  normal  animals  (p.  257). 

Naunyn^  observed  that  rabbits  might  be  artificially  warmed 
for  thirteen  days  so  that  an  average  body  temperature  of  41.5° 
was  maintained  without  any  parenchymatous  or  fatty  degen- 
eration taking  place.  The  animals  were  supplied  with  ample 
food,  water,  and  a  sufficient  supply  of  air.  Naunyn  found  that 
the  red  blood-cells  of  rabbits  and  dogs  remained  intact  even  at 
a  body  temperature  of  42°.     Welch^  noticed  fatty  but  no  paren- 


^Litten:  "Virchow's  Archiv,"  1877,  Bd.  Ixx,  p.  10. 
2  Naunyn:  "Archiv  fiir  ex.  Path,  und  Pharm.,"  18S 
^  Welch:   "Medical  News,"  1888,  vol.  lii,  p.  403. 


I,  Bd.  xviii,  p.  49. 


METABOLISM  IN  FEVER.  33 1 

chymatous  change  in  the  tissues  of  rabbits  after  exposure  to  high 
temperature  for  at  least  a  week.  One  rabbit  which  had  been 
subjected  to  high  temperature  for  four  days  was  inoculated 
with  the  bacilli  of  the  swine  plague  and  died  in  thirty-six  hours 
showing  extreme  fatty  changes  in  the  heart  and  other  organs. 

Ziegler^  discovered  degenerative  changes,  both  parenchy- 
matous and  fatty,  on  artificially  warming  rabbits.  The  experi- 
ment was  continued  in  one  case  for  twenty-nine  days.  He 
found,  however,  a  great  reduction  (30  per  cent,  and  more)  in  the 
quantity  of  hemoglobin  in  his  rabbits.  It  may  well  be  a  question 
whether  the  fatty  change  noticed  in  the  liver  and  muscles  was 
not  due  to  anemia  instead  of  to  the  hyperthermia.  Since  fatty 
infiltration  is  kno^vn  to  be  caused  by  dyspnea,  which  frequently 
terminates  life  in  fever,  one  might  investigate  this  subject  to  see 
whether  parenchymatous  change  in  fever  is  not  solely  due  to  the 
toxins,  and  fatty  change  to  the  anaerobic  cleavage  of  materials 
in  the  cells,  which  always  induces  fatty  infiltration  (p.  304). 

Ever  since  the  experiments  of  von  Leyden^  a  retention  of 
water  in  fever  has  been  assumed.  It  has  also  been  shown  that 
there  is  a  retention  of  sodium  chlorid  within  the  body.  The 
intimate  relation  between  the  retention  of  water  and  salt  has 
been  beautifully  demonstrated  by  Sandelowsky^  in  Liithje's 
clinic.  Thus  during  the  period  of  high  fever  in  pneumonia,  a 
gain  in  weight,  a  sodium  chlorid  retention,  and  a  dilution  of  the 
organic  contents  of  the  blood  usually  went  hand  in  hand.  After 
the  crisis,  however,  a  loss  in  weight,  a  loss  of  chlorid,  and  a 
more  concentrated  blood  resulted.  Similar  conditions  were 
found  in  scarlet  fever.^  Sandelowsky  observed  that  when  sod- 
ium chlorid  was  given  to  a  patient  convalescent  from  pneumonia, 
it  was  not  as  readily  eliminated  by  the  kidney  as  it  would  have 
been  normally.     From  this  he    concluded    that    a   disturbed 

'Zieglcr:    "Kongrcss  fur  innere  Medizin,"  1895,  Bd.  xiii,  p.  345. 
M'on  Leyden:  ■"Deutschcs  Archiv  fiir  klin.   Med.,"  1869,  Bd.  v,  p.  273. 
'  Sandelowsky:  "Deutsches  Archiv  fur  klin.  Med.,  "  1909,  Bd.  xcvi,  j).  445. 
*  Oppenheimer  and  Rciss:  Ibid.,  p.  464. 


332 


SCIENCE    OF   NUTRITION. 


renal  condition  existed  during  fever,  and  was  not  wholly  re- 
stored to  the  normal  after  the  crisis.  This  brought  about 
sodium  chlorid  retention,  which  in  turn  caused  water  retention, 
that  the  normal  osmotic  conditions  might  be  preserved.  This 
accounts  for  the  gain  in  body-weight  and  the  loss  in  the  con- 
centration of  the  blood  in  fever. 

As  regards  the  etiology  of  fever,  various  attempts  have  been 

made  to  identify  a 
single  factor  which 
would  cause  the  high 
temperature. 

Krehl  and  Mat- 
thes^  find  that  human 
urine  during  fever 
contains  an  increased 
quantity  of  albu- 
moses  which  have 
been  shown  to  pos- 
sess a  decidedly  toxic 
action  when  intro- 
duced into  animals. 
Klemperer^  denies 
that  these  albumoses 
have  any  toxic  action 
and  asserts  that  the 
results  were  due  to 
impurities  in  pre- 
paration. In  other  respects  the  urine  has  generally  been  found 
to  be  of  normal  character.  Thus  Mohr^  finds  that  the  relation 
C  to  N  in  the  urine  is  unchanged  from  the  normal,  which 
indicates  that  there  is  no  qualitative  change  in  the  character  of 
the  general  protein  metabolism. 

'  Krehl  and  Matthes:   "Archiv  fiir  klinische  Medizin,"  1895,  Bd.liv,p.  501. 
*  Klemperer:    " Naturforscherversammlung,"  1903,  2,  ii,  p.  67. 
^Mohr:   "Zeitschrift  fiir  klinische  Medizin,"  1904,  Bd.  lii,  p.  371. 


GRAM 
PURIN  BASES 
0.07 


0.05 


Fig. 


II. — Resection  of    knee-joint  for  tubercular 
arthritis. 


METABOLISM   IN   FEVER. 


333 


However,  there  is  a  very  noteworthy  record  made  by  A.  R. 
MandeP  that  the  rise  of  temperature  in  so-called  aseptic  or 
surgical  fevers  is  accompanied  by  a  large  increase  in  the  purin 
bases  in  the  urine  of  patients  fed  with  milk.     The  temperature 
rises  and  falls  with  the  quantity  of  purin  bases  eliminated.     The 
uric  acid  elimination  is  reduced  (p.  346).     These  relations  are 
illustrated  in  Fig.  11, — a  case  of  resection  of  the  knee-joint  for 
tubercular  arthritis.    The  temperatures  recorded  represent  the 
average  of  observations  made  every  three  hours  during  the  day. 
That  the  purin  bases  can  be  the  cause  of  the  rise  of  temper- 
ature is  indicated  by  the 
experiments  of  Burian  and       .-temr  r 
Schur,^  who    found    that 
when   nucleoprotein    was 
administered        intraven- 
ously   to    a    dog,    a   rise 
of    temperature  followed. 
Mandel    showed    that    a 
subcutaneous  injection  of 
40  milligrams  of  xanthin 
caused  a  marked  rise  in 
the  temperature  of  a  mon- 
key, and  that  the  adminis- 
tration of  a  strong  decoc- 
tion of  60  grams  of  coffee 


GRAM 
PURIN  BASES 
0.06 


Fig.    12.- 


-Case   A.  M.  Given  decoction  of 
60  giTis.  co£Fee. 


(containing  trimethyl-xanthin)  to  a  man  unused  to  coffee  drink- 
ing was  foUowed  by  a  febrile  temperature.     This  is  shown  in 

Fig.  12. 

Another  research  available  in  this  connection  is  that  of 
von  Jaksch,^  who  noted  that  the  purin  bodies  in  the  urine  of 
tuberculous  patients  may  increase  from  a  normal  equivalent 
of  4.4  per  cent,  of  the  total  nitrogen  excreted,  to  one  representing 

1  Mandel:   "American  Journal  of  Physiology,"  1904,  vol.  x,  p.  452. 

»  Burian  and  Schur:   "Pfluger's  Archiv,"  1901,  Bd.  Ixxxvii,  p.  239. 

» Von  Jaksch:   "Zcitschrift  fur  klinische  Medizin,"  1902,  Bd.  xlvu,  p.  i. 


334  SCIENCE   OF  NUTRITION. 

II. 3,  or  even  17.39  P^^  cent.  Also  Benjamin^  reports  a  case  of 
typhoid  where  the  urine  contained  the  large  quantity  of  o.i 
gram  of  purin  bases  with  0.54  gram  of  uric  acid.  Erben^  and 
Leathes^  report  that  the  output  of  uric  acid  is  always  increased 
during  high  fever.  Erben  also  finds  that  the  content  of  the 
urine  in  xanthin  bases  and  amino-acids  is  greatly  augmented 
in  measles  and  chicken-pox;  and  that  the  xanthin  bases  are 
also  increased,  though  to  a  lesser  extent,  in  scarlet  fever  and 
typhoid.  Mandel*  has  fed  monkeys  with  bananas  and  xanthin 
and  witnessed  a  rise  in  body  temperature,  and  has  noticed  that 
if  sodium  salicylate  be  given  at  the  same  time  no  rise  in  tempera- 
ture occurs.  Ott^  reports  that  guanin,  adenin,  and  hypoxanthin 
cause  an  elevation  of  temperature  in  rabbits,  while  uric  acid  does 
not. 

Mandel  believes  that  the  purin  bases  liberated  through  the 
toxic  destruction  of  tissue  may  play  a  considerable  part  in  pro- 
ducing the  temperatures  noted  in  fever.  It  is  evident  that  the 
use  of  purin-free  milk  instead  of  purin-containing  meat  has  its 
scientific  justification. 

It  would  indeed  be  a  most  striking  fact  if  it  should  be  found 
that  the  cause  of  the  febrile  temperature  lies  in  the  effect  of  purin 
bases  on  the  heat-regulating  apparatus  of  the  mid-brain  acting 
through  the  vasomotor  system.  Antipyretics  do  not  lower  body 
temperature  in  the  normal  organism  in  man.  Is  their  action 
merely  to  nullify  the  activity  of  purin  bases  upon  the  nerve 
centers?  Future  research  alone  can  decide  this.  Such  con- 
jectures indicate  the  extraordinary  field  which  lies  open  to  the 
investigator  in  clinical  medicine. 

^Benjamin:   "Salkowski's  Festschrift,"  1904,  p.  61. 

*  Erben:   "Zeitschrift  fiir  Heilkunde,"  1904,  Bd.  xxv,  p.  ^^. 
'Leathes:    "Journal  of  Physiology,"  1907,  vol.  xxxv,  p.  205. 

*  Mandel:    "American  Journal  of  Physiology,"  1907,  vol.  xx,  p.  439. 
^Ott:   "The  Medical  Bulletin"  (Medico-Chir.  College),  October,  1907. 


CHAPTER  XIV. 
PURIN  METABOLISM,-GOUT. 

Uric  acid  was  discovered  in  urinary  calculi  by  Scheele  in 
1776,  and  was  found  to  be  present  in  gouty  concretions  by  Wol- 
laston  in  1797.  It  has  since  been  the  subject  of  investigations 
almost  without  number,  and  of  theoretical  speculation  beyond 
that  of  any  other  chemical  substance  described  in  medical 
literature.  The  older  work  concerning  the  excretion  of  uric  acid 
is  almost  valueless  on  account  of  the  inadequacy  of  the  chemical 
methods  of  the  times.  Accurate  determinations  of  uric  acid 
date  from  the  introduction  of  a  new  method  of  analysis  by 
Salkowski  in  1882. 

The  newer  researches  are  also  based  on  more  exact  chemical 
knowledge  of  the  precursors  of  uric  acid.  Much  valuable  infor- 
mation has  been  gathered  as  regards  the  normal  method  of  produc- 
tion of  uric  acid,  although  it  will  be  seen  that  on  the  pathological 
side  there  is  little  beyond  the  conjectural  to  reward  the  student. 

Emil  Fischer^  grouped  together  uric  acid,  hypoxanthin, 
xanthin,  adenin,  and  guanin  as  bodies  whose  varying  structure 
depended  upon  slight  changes  around  the  chemical  nucleus  of  a 
substance  called  purin.  Purin,  according  to  Fischer,  may 
occur  in  the  body,  but  on  account  of  its  ready  decomposability, 
has  not  been  discovered  there. 

The  relations  between  the  purin  bodies  may  be  judged  from 
the  following  formulae : 

Purin QH.N^ 

Hypoxanthin C5H4N4O 

Xanthin C5H4N/J3 

Uric  acid CjH.N.O, 

Adenin C:,H,N«NH, 

Guanin. CjHaNjONHj 

'Fischer:  "Berichte  dcr  deutschen  chcmischen  Gcseilschaft,"  1899,  Bd. 
xxxii,  p.  435. 

335 


336  SCIENCE    OF   NUTRITION. 

Hypoxanthin,  xanthin,  and  uric  acid  are  respectively  mono-, 
di-,  and  tri-oxypurin.  Adenin  is  aminopurin,  and  guanin  is 
aminohypoxanthin.  It  is  evident  that  uric  acid  is  the  most 
highly  oxidized  product  of  the  series,  and  might  readily  arise 
from  the  oxidation  of  hypoxanthin  and  xanthin.  It  is  also  ap- 
parent that  by  supplanting  the  NHg  group  in  adenin  and  guanin 
by  O,  they  would  be  converted  into  hypoxanthin  and  xanthin 
respectively,  and  that  from  these  substances  uric  acid  might 
arise  through  oxidation. 

These  reactions  may  be  thus  expressed : 

HN— CO  HN CO  HN CO 

II                                 II  II 

NH2— C     C— NH    >     C  =  0  C— NH     >     C  =  OC— NH 

II      II      y^^                   I            II      ^^^                 I  II      /^^ 

N— C— N  HN C— N  HN C— NH 

Guanin,  Xanthin,  Uric  acid, 

amino-oxypurin.  dioxypurin.  trioxypurin. 

A 

N  =  CNH,  HN— CO 

II  II 

HC     C— NH      >  HC     C— NH 

II      II        >^^  II       II      >^^ 

N— C— N  N— C— N 

Adenin,  Hypoxanthin, 

aminopurin.  oxypurin. 

The  deamination  of  guanin  and  adenin  is  accomplished  by 
hydrolysis  and  may  occur  in  the  absence  of  oxygen,  whereas  the 
conversion  of  hypoxanthin  into  xanthin  and  the  latter  into 
uric  acid  are  true  processes  of  oxidation. 

For  greater  detail  of  the  chemistry  of  purins,  the  reader  is 
referred  to  any  text-book  on  physiological  chemistry.^  The 
four  precursors  of  uric  acid,  hypoxanthin,  xanthin,  adenin,  and 
guanin  are  collectively  called  the  purin  bases.  The  general 
term,  purin  bodies,  includes  uric  acid  also. 

Since  Salomon  discovered,  in  1880,  that  purin  bases  exist 

^Consult  also  Mendel:  "The  Formation  of  Uric  Acid,"  Harvey  Society 
Lecture,  "  Journal  of  the  American  Medical  Association,"  1906,  vol.  xlvi,  p.  843. 


PURIN   METABOLISM. — GOUT. 


Z2>1 


in  the  nucleins  which  are  present  in  the  nuclei  of  cells,  a  great 
deal  of  work  has  been  done  to  explain  the  chemical  nature  of 
these  nuclear  constituents.  A  summary  of  the  products  which 
can  be  obtained  from  nucleoproteins  is  as  follows: 


Nucleoprotein 


Protein 


Nuclein 


Protein 


Nucleic  acid 


Carbohydrates. 

Pentoses, 

Hexoses, 

Glucothionic  acid,' 

a  non-reducing  sub- 
stance which  yields 
levxilinic  acid. 


Phosphoric  acid. 


Bases. 


Adenin,      \ 
Guanin,     / 

Thymin, 
Cytosin, 
Uracil, 


Purin  bases. 


Pyrimidin 
bases. 


The  formulae  of  the  pyrimidin  bases  are : 


HN— CO 

I    I 

OC    CH 

I       II 

HN— CH 

Uracil. 


HN  =  CNH, 

I        I 
OC    CH 

I       II 

HN— CH 

Cytosin. 


HN— CO 

I        I 
OC    CCH, 

I      II      • 
HN— CH 
Thymin. 


Kossel  and  SteudeP  point  out  the  fact  that  the  purin  bases 
contain  the  pyrimidin  nucleus,  and  that  cytosin,  for  example, 
needs  only  cyanic  acid,  CONH,  and  an  atom  of  oxygen,  to 
convert  it  into  uric  acid. 

They  query  whether  the  pyrimidin  bases  are  precursors  or 
metabolized  products  of  the  purins,  but  the  question  is  still  un- 
settled.' 

*  Mandel  and  Levene:  "Zeitschrift  fiir  physiologischc  Chcmie,"  1906,  Bd. 
xlvii,  p.  151. 

*  Kossel  and  Steudel:  "Zeitschrift  fiir  physiologischc  Chemie,"  1903,  Bd. 
xxxviii,  p.  49. 

*  Consult  Abderhalden:  "Lchrbuch  der  physiologischcn  Chcmie,"  1909,  p. 
381- 

22 


338  SCIENCE   OF  NUTRITION. 

Horbaczewski  ^  was  the  first  to  note  that  the  ingestion  of 
nucleins  largely  increased  the  uric  acid  in  the  urine.  Food  free 
from  nuclein  has  not  this  effect.  He  also  found  that  if  fresh 
spleen  pulp,  which  contains  no  uncombined  purin  bases,  be 
permitted  to  putrefy,  xanthin  and  hypoxanthin  made  their  ap- 
pearance. If  now  the  pulp  was  shaken  in  the  air,  uric  acid  was 
formed  from  the  oxidation  of  the  bases. 

Spitzer^  found  that  when  air  was  passed  through  aqueous 
extracts  of  spleen  and  liver  digested  at  40°  and  with  exclusion 
of  putrefaction,  uric  acid  was  produced.  The  quantity  of 
purin  bases  present  decreased  with  the  increased  formation 
of  uric  acid.  Purin  bases  added  to  such  a  digest  were  converted 
into  uric  acid,  hypoxanthin,  and  xanthin  readily  and  almost 
completely,  and  guanin  and  adenin  with  greater  difficulty. 
This  work  established  the  presence  of  oxidizing  enzymes,  the 
xanthin  oxidazes,  which  could  act  on  the  purin  bases  in  the 
organism  converting  them  into  uric  acid. 

Minkowski^  has  shown  that  if  a  man  be  given  hypoxanthin, 
the  quantity  of  uric  acid  increases  in  his  urine.  He  also  showed 
that  if  a  man  ingest  thymus  gland,  the  nuclein  of  which  yields 
principally  adenin,  the  amount  of  uric  acid  is  increased  in  the 
urine.  If  the  thymus  be  given  to  a  dog,  the  uric  acid  plus 
allantoin  elimination  is  increased.  AUantoin  is  an  oxidation 
product  of  uric  acid  more  frequently  found  in  dog's  than  in 
human  urine.  Minkowski  discovered  finally  that  adenin,  when 
administered  to  a  dog,  did  not  increase  the  uric  acid  elimination, 
and  was  not  excreted  as  such,  but  on  autopsy  of  the  dog  the 
uriniferous  tubules  were  found  to  contain  crystals  the  chemical 
structure  of  which  showed  them  to  be  aminodioxypurin.  In 
other  words,  adenin  administered  combined  in  nucleic  acid 
loses  its  amino  (NHg)  group,  receives  three  atoms  of  oxygen, 

^  Horbaczewski :  "Sitzungsberichte  der  Wiener  Academie  der  Wissen- 
schaft,"  1891,  Bd.  c,  Abth.  iii,  p.  13. 

^  Spitzer:   "Pfliiger's  Archiv,"  1899,  Bd.  Ixxvi,  p.  192. 

^  Minkowski:   "Archiv  fur  ex.  Path,  und  Pharm.,"  1898,  Bd.  xli,  p.  375. 


PURIN  METABOLISM. — GOUT.  339 

and  is  thereby  converted  into  uric  acid ;  adenin  administered  as 
such  receives  two  atoms  of  oxygen  but  docs  not  lose  its  NHj 
group  at  the  point  for  the  attachment  of  the  third  atom  of  oxygen. 
This  work  attests  a  var}-ing  behavior  of  purin  bodies  in  accord- 
ance with  their  method  of  chemical  union  with  other  substances, 
and  offers  a  suggestive  key  to  certain  relations  observed  in  gout 
(p.  353).  When  theophyllin,  caffein,  and  theobromin,  the 
methylated  purins  found  in  tea,  coffee,  and  cocoa,  are  ingested 
they  are  not  oxidized  to  uric  acid,  but  they  increase  the  purin 
bases  in  the  urine. ^ 

The  original  investigations  of  Horbaczewski  have  recently 
been  considerably  extended  by  Schittenhelm  and  by  Walter 
Jones,  especially  in  regard  to  their  explanation  along  lines  of 
enzymotic  activity. 

Jones  and  Partridge^  find  that  although  the  great  majority 
of  the  organs  of  the  body,  when  self-digested  at  40°  (autolysis), 
convert  guanin  and  adenin  into  xanthin  and  hypoxanthin, 
presumably  through  the  action  of  enzymes,  extracts  of  the  spleen 
of  the  pig  cannot  convert  guanin  into  xanthin,  although  they 
can  convert  adenin  into  hypoxanthin.  Jones  therefore  con- 
cludes that  an  enzyme,  guanase,  which  normally  removes  the 
NHj  group  and  replaces  it  with  O,  is  wanting  in  the  pig's 
spleen,  while  adenase,  the  enzyme  acting  on  adenin  in  a  similar 
fashion,  is  present  there.     Such  a  reaction  would  read : 

C5H3N4NH2+  H2O  =  CsI^H.O  -I-  NH3 
Adenin.  Hypoxanthin. 

Investigating  the  subject  further,  the  authors  found  that  the 
pancreas  contained  the  enzyme,  guanase,  which  converts  guanin 
into  xanthin. 

The  behavior  of  the  livers  of  different  animals  has  been 
investigated  by  Jones  and  Austrian.^     In  cattle  livers,  for  ex- 

'Kruger  and  Schmid:  "Zeitschrift  fur  physiologische  Chcmic,"  1901,  Bd. 
xxxii,  p.  104. 

'  Jones  and  Partridge:  Ibid.,  1904,  Bd.  xlii,  p.  .343;  sec  also  Lcvcnc:  "Amer- 
ican Journal  of  Physiology,"  1904,  vol.  xii,  p.  276. 

'  Jones  and  Austrian:  "Zeitschrift  fiir  physiologische  Chemie,"  1906,  Bd. 
xlviii,  p.  no. 


34Q  SCIENCE   OF  NUTRITION. 

ample,  adenase,  guanase  and  xanthin  oxidase  are  present, 
whereas  in  dog  livers  guanase  is  present,  adenase  occurs  in 
traces  only,  and  no  xanthin  oxidase  whatever  has  been  found. 
Hence  catde  livers  may  form  uric  acid  from  adenin  and  guanin, 
while  dog  livers  only  convert  guanin  into  xanthin  and  the  other 
processes  are  arrested.  The  process  is  thus  graphically  repre- 
sented : 

Dog  Livers. 
Guanin.  Adenin. 


^ 

Cattle  Livers. 

Guanin. 

Adenin. 

m 

S 

i 

3 

^ 

g 
■d 

Uric  Acid-^— 

— Xa 

nthin-*^ — 

—Hypo 

xanthin. 

Uric  Acid Xanthin HypoxanthLa. 

Xanthin  oxidase  present.  Xanthin  oxidase  and  adenase  absent. 

Furthermore  these  authors  find  that  guanase  is  absent  from 
pigs'  livers,  while  adenase  and  xanthin  oxidase  are  present.  It 
is  interesting  that  Mendel  and  MitchelP  have  found  in  the  liver 
of  the  embryo  pig  at  an  early  age  the  same  specific  enzymes  as 
characterize  the  liver  of  the  adult  animal.  There  was,  however, 
a  considerable  delay  in  the  appearance  of  the  enzyme  which 
oxidizes  uric  acid  (see  below).  It  is  a  curious  phenomenon  that 
pigs  suifer  from  guanin  gout.  Their  normal  urines  contain  uric 
acid,^  but  it  may  be  surmised  that  in  guanin  gout  the  enzyme 
guanase  is  wanting. 

Schittenhelm^  reports  that  human  livers  have  the  power  to 
form  uric  acid  from  added  purins  and  he  believes  that  the  power 
to  oxidize  uric  acid  exists. 

Lauder  Brunton*  says  that  Stockvis,  of  Amsterdam,  in 
i860,  found  that  crushed  tissue  had  the  power  to  destroy  uric 
acid.  This  question  has  recently  come  into  prominence  and 
it  has  been  shown  that  different  organs  have  different  powers 

^Mendel  and  Mitchell:  "American  Journal  of  Physiology,"  1907,  vol.  xx, 
p.  97. 

^  Schittenhelm  and  Bendix:  "  Zeitschrift  f iir  physiologische  Chemie,"  1906, 
Bd.  xlviii,  p.  140. 

^  Kiinzel  and  Schittenhelm:  "  Zentralblatt  fiir  StoiJwechsel,"  1908,  Bd.  iii, 
p.  721. 

*  Lauder  Brunton:   "  Centralblatt  fiir  Physiologie,"  1905,  Ed.  xix,  p.  5. 


PURIN   METABOLISM. — GOUT.  341 

in  this  regard,  and  that  the  same  organ  in  animals  of  different 
species  may  behave  quite  differently. 

Wiener^  showed  that  dog's  liver  and  pig's  liver  destroyed  uric 
acid,  whereas  calf's  liver  had  less  power  to  do  so,  or  none  at  all. 
The  kidney  pulp  of  various  animals  also  destroyed  uric  acid. 

Schittenhelm^  finds  that  in  cattle  the  spleen,  lungs,  liver, 
intestine,  and  kidney  have  the  powder  of  converting  purin  bases 
into  uric  acid  in  the  presence  of  a  constant  oxygen  supply. 
He  finds  a  complete  transformation  of  adenin,  as  follows: 
adenin,  hypoxanthin,  xanthin,  uric  acid.  Guanin  in  like  man- 
ner becomes  xanthin  and  this  again  is  converted  into  uric  acid. 
He  finds  also  that  extracts  of  the  spleen,  intestines,  and  lungs 
have  no  power  to  destroy  uric  acid  as  formed  within  them,  but 
that  the  kidney,  muscle,  and  liver  extracts  possess  the  power  to 
destroy  the  new-formed  uric  acid. 

Schittenhelm^  in  another  paper  finds  that  kidney  extracts 
from  cattle,  through  which  oxygen  is  passed,  may  completely 
destroy  uric  acid  through  a  uricolytic  enzyme. 

It  has  been  sho\Mi  by  Pfeiffer*  that  the  pulps  of  human 
kidneys  and  pigs'  kidneys  have  the  power  to  destroy  uric  acid 
completely,  while  dogs'  kidneys  have  only  a  limited  capacity 
in  this  regard. 

Almagia^  finds  that  in  the  horse  the  greatest  power  of  uric 
acid  destruction  is  possessed  by  the  liver,  and  then  follow  in 
order  of  diminishing  activity  the  kidney,  lymphatic  glands, 
leukocytes,  muscles,  bone-marrow,  spleen,  and  thyroid.  In 
other  organs,  like  the  brain  and  the  pancreas,  the  conditions  are 
such  as  indicate  a  non-destruction  of  uric  acid,  which  is  produced 
by  the  oxidation  of  purin  bases  within  them. 

Summarizing  these  results  it  may  be  said  that  nucleic  acid 

'Wiener:    "Archiv  fur  ex.  Path,  und  Pharm.,"  1899,  Bd.  xlii,  p.  375. 
^Schittenhelm:    "Zeitschrift  fur  physiologische   Chemie,"    1905,  Bd.  xlv, 

P-  145- 

*Schittenhelm:'  Ibid.,  1905,  Bd.  xlv,  p.  161. 

*Pfeiffer:   "Hofmeister's  Beitrage,"  1905,  Bd.  vii,  p.  463- 

'Almagia:    "Hofmeister's  Beitrage,"  1905,  Bd.  vii,  ]i.  459. 


342  SCIENCE   OF   NUTRITION. 

may  be  broken  up  by  nuclease,  a  ferment  found  in  all  tissue.  On 
the  liberation  of  the  purin  bases,  guanin  and  adenin  are  deamin- 
ized  by  guanase  and  adenase  wherever  these  enzymes  are 
found.  Oxidizing  enzymes,  the  xanthin  oxidases,  now  convert 
hypoxanthin  and  xanthin  into  uric  acid,  while  a  uricolytic  fer- 
ment of  varying  potency  in  different  tissues  and  in  different 
animals  may  break  up  and  destroy  the  uric  acid.  That  pro- 
cesses akin  to  these  go  on  within  the  living  organs  of  the  body  is 
now  generally  believed,  and  the  following  animal  experiments 
tend  to  confirm  this  doctrine,  although  it  will  become  evident 
that  the  uricolytic  power  of  kidney  extracts,  so  frequently  men- 
tioned above,  appears  to  be  entirely  overshadowed  in  the  living 
kidney  by  the  function  of  uric  acid  elimination. 

It  has  already  been  stated  that  the  ingestion  of  hypoxanthin 
by  a  man  increased  the  uric  acid  output  in  the  urine.  It  has 
long  been  known  that  if  uric  acid  be  given  per  os,  it  may  in 
greater  part  be  converted  into  urea,  and  in  part  eliminated  in 
the  urine.  The  quantity  eliminated  varies  in  different  animals. 
Salkowski^  finds  that  uric  acid  given  to  dogs  is  mostly  eliminated 
as  urea,  although  17.7  per  cent,  appears  in  the  urine  in  the  form 
of  allantoin.  When  uric  acid  is  given  to  rabbits  the  urine  con- 
tains urea,  allantoin,  and  some  uric  acid.  Mendel  and  White  ^ 
found  that  allantoin  was  eliminated  in  the  urine  of  cats  and 
dogs  after  intravenous  injection  of  urates.  The  relationship 
between  uric  acid  and  allantoin  is  evident  from  the  following 
formulas : 

HN CO  HN CO 


CO      C— NH 

CO 

H2N 

^CO 

^CO 

N C— NH 

HN 

3H— NH 

Uric  acid. 

Allan 

toin. 

It  is  usually  believed  that  uric  acid  is  largely  destroyed  in 

^Salkowski:  "Zeitschrift  fiir  physiologische  Chemie,"  1902,  Bd.  xxxv. 
P-  495- 

^Mendel  and  White:  "American  Journal  of  Physiology,"  1904,  vol.  xii, 
p.  85. 


PURIN   METABOLISM. — GOUT,  343 

animals  such  as  cats,  dogs,  and  rabbits,  and  that  a  portion  of 
an  intermediary  product  of  oxidation,  allantoin,  appears  in  the 
urine.  However,  Wiechowski^  states  that  uric  acid  digested 
with  the  pulp  of  dog's  liver  is  oxidized  completely  into  allantoin 
and  no  further;  and  also  that  uric  acid  injected  subcutaneously 
into  a  dog  is  almost  completely  eliminated  as  allantoin  in  the 
urine.  He  does  not  show  that  purin  bases  ingested  normally 
behave  in  the  same  manner. 

Schittenhelm  and  Bendix"  have  injected  rabbits  subcutane- 
ously and  intravenously  with  guanin,  and  have  found  uric  acid 
in  greatly  increased  quantity  in  the  urine,  together  with  xanthin, 
which  is  normally  absent  in  rabbits.  The  experiment  indicates 
the  metabolism  of  guanin  intra  vitam,  according  to  processes 
already  obsen^ed  in  vitro.  If  an  Eck  fistula,  which  excludes 
the  portal  blood  from  the  liver,  be  made  in  a  dog,  uric  acid  ap- 
pears in  considerable  quantity  in  the  urine,  which  indicates 
that  uric  acid  is  normally  oxidized  in  the  dog's  liver.^ 

Burian  and  Schur,*  after  careful  perusal  of  the  literature 
and  of  their  own  work,  came  to  the  conclusion  that  each  variety 
of  animal  had  a  specific  capacity  for  burning  purin  bodies 
ingested.  They  found  a  constant  elimination  in  dog's  urine 
of  one-twentieth  part  of  the  purins  ingested,  one-sixth  part  in  the 
case  of  rabbits,  and  one-half  in  the  case  of  man.  They  describe 
how  Minkowski,  after  giving  a  man  hypoxanthin,  saw  that 
48.6  per  cent,  of  it  was  eliminated  as  uric  acid;  how  Burian 
repeated  the  experiment  with  the  result  that  46.2  per  cent, 
appeared  as  uric  acid;  how  the  subject  of  the  last  experiment 
eliminated  51.1  and  53.8  per  cent,  of  the  purins  contained  in  a 
meat  diet,  and  52.6  and  52.9  per  cent,  of  those  contained  re- 

'  Wiechowski :  " Hof meister's  Beitragc,"  1907,  Bd.  ix,  p.  295;  1908,  Bd. 
xi,  p.  109. 

^  Schittenhelm  and  Bendix:  "Zeitschrift  fur  physiologische  Cheinic,"i905, 
Bd.  xliii,  p.  365. 

'  Hahn,  Massen,  Nencki,  and  Pawlow:  "Archivfur  ex.  Path,  und  Pharm.," 
1893,  Bd.  xxxii,  p.  191. 

*  Burian  and  Schur:   "Pfluger's  Archiv,"  1901,  Bd.  Ixxxvii,  p.  239. 


344  SCIENCE   OF  NUTRITION. 

spectively  in  calf's  liver  and  calf's  spleen.  Therefore,  Burian 
and  Schur  multiplied  the  purin  excretion  of  a  man  by  two  and 
of  a  dog  by  twenty  in  order  to  determine  the  total  purin  metabo- 
lism. They  called  these  numbers  the  integral  factors  of  purin 
excretion.  The  cause  of  the  size  of  the  integral  factor  will  be 
discussed  later. 

It  has  been  made  clear  that  the  purin  bodies  may  be  derived 
from  ingested  nucleins,  but  this  cannot  be  the  only  source, 
since  purins  are  found  in  the  urine  during  starvation  and  on 
a  diet  free  from  purins.  This  indicates  a  constant  production 
of  these  substances  in  metabolism,  it  has  been  thought,  through 
the  destruction  of  cell  nuclei.  Uric  acid  and  purin  bases  from 
this  source  have  been  termed  endogenous  by  Burian  and  Schur, 
in  contradistinction  to  those  which  are  eliminated  after  the  in- 
gestion of  nuclein-containing  food,  which  are  called  exogenous. 

Burian  and  Schur^  also  established  the  fact  that  while  the 
endogenous  uric  acid  elimination  varied  between  0.3  and  0.6 
gram  daily,  according  to  the  individual,  it  did  not  vary  in 
the  same  individual  but  was  a  constant  factor  of  his  metabo- 
lism. 

A  purin-free  diet  is  obtained  by  giving  such  articles  of  food 
as  milk,  eggs,  bread,  potatoes,  fats,  and  sugars,  iione  of  which 
contain  nuclear  material  which  forms  exogenous  purins  in  the 
body.  Burian  and  Schur  found  that  on  such  a  diet  the  uric 
acid  elimination  was  entirely  independent  of  the  quantity  of 
protein  ingested.  It  has  been  demonstrated  by  Rockwood^ 
that  the  endogenous  uric  acid  elimination  is  independent  of  the 
calorific  value  of  the  diet.  Addition  of  500  calories  contained 
in  maple  sugar  to  a  diet  containing  2500  calories  did  not  affect 
the  excretion  of  uric  acid.  Rockwood's  experiments  extended 
over  a  long  period  of  time.  His  individuals  were  nourished  on 
milk,  eggs,  white  bread,  crackers,  cheese,  apples,  and  butter. 
The  constancy  of  the  uric  acid  output  in  the  same  individual  is 

^  Burian  and  Schur:  Loc.  cit. 

^Rockwood:    "American  Journal  of  Physiology,"  1904,  vol.  xii,  p.  38. 


PURIN  METABOLISM. — GOUT.  345 

seen  in  the  following  table, — in  one  case  the  record  covering 
nearly  a  year: 

TABLE  SHOWING  THE  CONSTANCY  OF  THE  DAILY  ENDOG- 
ENOUS URIC  ACID  EXCRETION  IN  THE  SAME  INDIVIDUAL 
(TWO  SUBJECTS). 

Person,  A.  Date,  1903.  N  in  Ukine,  Grams.        Uric  Acid,  Grams. 

Januan' ii-99  0.308 

February ii-SS  °-3°S 

March ii-iS  o-S^S 

May 12.63  0'32i 

July 12.68  0.313 

November 9.99  0.298 

Person,  B.         January i3-4i  0.478 

March 13-92  0.452 

This  total  shows  the  constancy  of  the  output  of  endogenous 
uric  acid  in  the  same  individual  during  a  long  period.  Here 
the  difference  in  the  behavior  of  two  individuals  might  possibly 
be  ascribed  to  a  personal  idios}Ticrasy  as  regards  the  uricolytic 
power  of  the  subject,  or  to  a  difference  in  the  capacity  of  pro- 
ducing uric  acid.  From  the  record  of  Chittenden's  ^  experiments, 
which  covered  a  period  of  twenty-one  months,  it  may  be  ob- 
served that  a  very  low  protein  diet  and  moderate  intake  of  food 
were  without  effect  on  the  output  of  uric  acid. 

Burian  and  Schur^  have  made  a  series  of  experiments  as 
regards  the  cause  of  the  ** integral  factor"  of  purin  metabolism, 
which  has  already  been  defined.  They  find  that  a  part  of  the 
endogenous  purins  are  burned  in  metabolism,  for  the  uric  acid 
elimination  in  the  dog  rises  largely  after  cutting  the  liver  from 
the  circulation  by  means  of  an  Eck  fistula.  They  note  that  no 
one  has  been  able  to  find  uric  acid  in  normal  blood.  They 
desired  to  see  if  uric  acid  would  accumulate  in  the  blood  if  the 
kidneys  were  both  extirpated.  No  such  result  followed  nephrec- 
tomy in  a  dog.  The  purin  bodies  were  apparently  completely 
burned.  They  then  extirpated  the  kidneys  and  ligated  the 
aorta  at  a  point  just  above  the  celiac  artery.    The  operation  cut 

'  Chittenden:    "Physiological  Economy  in  Nutrition,"  1904,  p.  24. 
^  Burian  and  Schur:   Loc.  cit. 


346  SCIENCE    OF   NUTRITION. 

off  the  liver  and  intestine  from  the  circulation.  Under  these 
circumstances  uric  acid  accumulated  in  the  blood  because  its 
destruction  was  not  accomplished  by  the  liver.  The  question 
arises:  If  the  normal  organism  can  completely  destroy  all 
purins,  why  should  a  definite  fraction  be  continually  eliminated 
in  the  urine?  Burian  and  Schur  believe  that  endogenous 
purins,  formed  in  the  tissues,  are  oxidized  therein  to  uric  acid, 
and  in  so  far  as  this  substance  is  carried  to  such  organs  as  the 
liver,  it  is  destroyed,  but  in  so  far  as  it  passes  through  the  renal 
arteries,  it  is  removed  by  the  kidney.  In  confirmation  of  this 
they  show  that  a  diuretic  which  increases  the  blood-fiow  to  the 
kidney  may  likewise  increase  the  uric  acid  elimination,  without 
affecting  the  other  nitrogenous  constituents  of  the  urine.  Pos- 
sibly the  fall  in  uric  acid  elimination  noted  by  Mandel  in  aseptic 
fever  (p.  332,  Fig.  11)  may  be  similarly  due  to  a  constriction 
of  the  renal  vessels  which  may  accompany  fever  (p.  319). 

Burian  and  Schur  conclude  that  of  the  mass  of  blood  which 
receives  uric  acid  from  the  tissues  in  man,  the  same  amount 
flows  through  the  organs  which  destroy  uric  acid  as  flows 
through  the  kidney,  and  hence  the  integral  factor  of  two.  On 
the  other  hand,  the  relation  between  the  volume  of  kidney 
blood  and  the  volume  of  blood  passing  through  the  organs 
which  destroy  uric  acid  in  dogs  must  be  as  i  :  20  in  order  to 
explain  the  integral  factor  twenty.  At  first  sight  this  does  not 
explain  why  exogenous  purins,  which  must  pass  from  the 
intestine  to  the  dog's  liver,  should  escape  complete  destruction 
in  that  organ.  Burian  and  Schur,  however,  have  shown  that 
whereas  uric  acid  given  per  os  is  almost  completely  destroyed 
in  the  dog,  the  purin  bases  or  the  products  of  nucleoprotein 
digestion  containing  them  apparently  pass  through  the  liver  to 
be  oxidized  to  uric  acid  elsewhere. 

The  liver  has  the  power  of  oxidizing  uric  acid  but  not  the 
purin  bases.  Hence  the  behavior  of  exogenous  purins  must  be 
exactly  the  same  as  if  they  arose  in  the  general  metabolism 
of  the  tissues  themselves  and  were  oxidized  to  uric  acid,  which 


PURIN  METABOLISM. — GOUT.  347 

was  then  carried  in  definite  fractions,  in  accordance  with  the 
relative  volume  of  the  blood  supply,  either  to  the  kidney  for 
elimination  or  to  the  organs  where  uric  acid  is  destroyed. 

This  explanation  of  the  cause  of  the  integral  factor  would 
explain  the  results  of  Loewi,^  which  showed  that  the  ingestion 
of  the  same  amount  of  nuclein-containing  food  by  different 
people  resulted  in  the  excretion  of  the  same  increased  quantity 
of  uric  acid  in  the  urine.  However,  Loewi  at  the  time  was 
inclined  to  believe  that  the  uric  acid  which  was  produced  in  the 
human  being  was  not  oxidized,  and  this  opinion  was  apparently 
confirmed  by  the  discovery  of  Soetbeer  and  Ibrahim,^  who 
found  that  the  subcutaneous  injection  of  uric  acid  in  man 
resulted  in  its  complete  elimination  in  the  urine.  This  view 
is  also  held  by  Wiechowski,^  who  has  further  shown  that 
allantoin  injected  subcutaneously  is  completely  eliminated  in 
human  urine  which  is  normally  free  from  it.  Schittenhelm^ 
criticizes  these  ideas  and  maintains  that  uric  acid  introduced  into 
the  blood  stream  might  behave  differently  from  uric  acid  arising 
from  purins  which  had  been  ingested.  In  the  latter  case  their 
partial  destruction  has  been  demonstrated. 

The  theory  of  a  fixed  integral  factor  is  not  supported  by 
Landau's^  experiments  upon  eight  human  beings.  Landau 
concludes  that  the  amount  of  the  elimination  of  exogenous 
purins  (mostly  uric  acid)  is  dilferent  in  different  individuals  and 
varies  between  37  and  91  per  cent,  of  the  purins  ingested.  He 
believes  that  these  differences  depend  on  differences  in  the  in- 
tensity of  the  uricolytic  power  of  the  various  subjects.  He  found 
that  the  quantity  of  exogenous  uric  acid  which  underwent 
oxidation  depended  upon  the  character  of  the  purin  material 

'  Loewi:   "Archiv  fiir  ex.  Path,  und  Pharm.,"  1900  ,Bd.  xliv,  p.  i. 

'Soetbeer  and  Ibrahim:  "Zeitschrift  fur  physiologische  Chemic,"  1902, 
Bd.  XXXV,  p.  I. 

'  Wiechowski :  "Archiv  fur  experimenteile  Path,  und  Pharm.,"  1909,  Bd. 
]x,  p.  185. 

*Kun/.el  and'Schittenhelm:  "Zentralblatt  fur  Stoffwechsel,"  1908,  Bd. 
iii,  p.  721. 

'  Landau:  "Deutsches  Archiv  fur  klinische  Medizin,"  1909,  Bd.  xcv,  p.  280. 


348  SCIENCE   OP  NUTRITION. 

given.  Hypoxanthin  when  ingested  uncombined  was  more 
largely  excreted  as  uric  acid  than  were  purins  contained  in 
nucleoprotein.  The  latter,  on  account  of  their  complicated 
structure,  were  only  slowly  broken  up  and  the  uric  acid  from 
them  appeared  less  rapidly  in  the  blood  than  if  free  purins  had 
been  ingested,  and  therefore  there  was  a  more  complete  oxida- 
tion and  a  reduced  elimination. 

The  source  of  the  endogenous  purins  has  been  the  cause  of 
considerable  speculation.  In  birds  there  is  a  large  synthetic  pro- 
duction of  uric  acid  in  the  liver,  for  Minkowski^  has  shown  that 
extirpation  of  the  liver  in  geese  leads  to  a  replacement  of  uric 
acid  by  ammonia  and  lactic  acid  in  the  urine.  In  the  developing 
organism  there  is  a  production  of  purins  for  the  construction  of 
the  nuclear  content  of  the  cells.  The  method  of  production  is 
entirely  conjectural. 

Ingestion  of  pyrimidin  bases  (p.  337)  has  failed  to  yield 
purins  in  the  organism.^ 

Burian^  has  investigated  the  source  of  the  endogenous  purins 
and  comes  to  the  conclusion  that  only  a  small  part  of  the  en- 
dogenous uric  acid  arises  from  the  nucleoproteins  of  cellular 
tissue  or  those  of  dead  leukocytes.  It  would  require  too  large 
a  destruction  of  tissue  to  provide  from  0.3  to  0.6  gram  uric 
acid  or  o.i  to  0.2  gram  purin  nitrogen  daily  in  the  urine  if  it 
all  arose  from  cell  nuclein. 

Burian  and  Schur's*  analyses,  showing  the  content  of  purin 
nitrogen  in  various  tissues,  are  given  below. 

TABLE  SHOWING  THE  QUANTITY  OF  PURIN  N  CONTAINED  IN 
100  GRAMS  OF  DIFFERENT  ANIMAL  TISSUES. 

Total  Purin  N.    N  in  Free  Pdrin  Bases. 

Meat 0.06  O-045 

Thymus 0.45  0.05 

Calf's  liver 0.12  "  0.033 

Calf's  spleen 0.16  0.046 

*  Minkowski:  "Archiv.  fur  experimentelle  Path,  und  Pharm.,"  1886,  Bd. 
xxi,  p.  41. 

^Steudel:  "Zeitschrift  fiir  physiologische  Chemie,"  1903,  Bd.  xxxix,  p.  136. 

^Burian:  "Zeitschrift  fiir  physiologische  Chemie,"  1905,  Bd.  xliii,  p.  532. 

^Burian  and  Schur:  "Pfluger's  Archiv,"  1900,  Bd.  Ixxx,  p.  308. 


PURIX  METABOLISM. — GOUT.  349 

To  obtain  the  amount  of  endogenous  uric  acid  present  in  the 
urine,  if  it  were  produced  by  the  destruction  of  nucleoproteins, 
it  would  be  necessary  to  destroy  completely  a  quantity  of 
nucleoprotein  equal  to  that  contained  in  more  than  loo  grams  of 
liver.  It  does  not  seem  possible  that  nuclein  destruction  or 
nuclein  metabolism  could  reach  this  extent. 

The  experiments  of  Burian^  consisted  in  perfusing  dog's 
muscles  with  blood  free  from  uric  acid.  He  noticed  that  after 
the  perfusion  of  such  blood  through  the  muscles,  uric  acid  was 
constantly  found  in  it.  If  the  muscle  was  caused  to  contract 
during  the  perfusion,  a  very  considerable  increase  in  the  quan- 
tity of  the  purin  bases  was  found  in  the  blood  and  there  was  an 
increase  in  the  quantity  of  these  bases  found  in  the  muscles 
themselves. 

Burian  concludes  that  in  the  resting  muscle  there  is  a  con- 
stant production  of  hypoxanthin  which  is  converted  into  uric 
acid  through  the  activity  of  the  xanthin  oxidase.  In  the  active 
muscle  there  is  a  greater  production  of  hypoxanthin  which  is 
not  completely  oxidized  on  account  of  a  local  oxygen  deficiency. 

It  had  been  found  by  many  previous  observers  that  exercise 
has  no  effect  on  the  purin  excretion  in  the  urine  of  twenty-four 
hours  in  man.  Burian,  however,  finds  a  large  increase  in  the 
purin  elimination  for  an  hour  or  two  after  severe  muscular 
exercise,  and  this  is  followed  by  a  compensatory  reduction  in 
the  output  during  those  subsequent  hours  which  represent  the 
interval  of  weariness  in  the  muscle. 

These  observations  were  confirmed  by  the  work  of  Rock- 
wood,^  who  saw  that  the  purin  excretion  was  less  during  the 
night  than  during  the  day,  and  by  the  work  of  Pfeil,^  who  found 
a  constant  morning  rise  in  the  output  of  purins  in  human  urine. 

These  facts  confirm  Burian's  contention  that  the  most 
general  source  of  endogenous  purins  is  a  constant  production 
of  hypoxanthin.  in  muscle,  a  production  which  varies  with  the 

'Burian:  Loc.  cit.  'Rockwood:  Loc.  cit. 

»PfeiI:    "Zeitschrift  fur  physiologische  Chcmic,"  1904,  Bd.  xl,  p.  i. 


35©  SCIENCE   OF   NUTRITION. 

individual  and  is  possibly  proportional  to  the  mass  of  his  mus- 
culature. Comparable  to  this  is  the  constant  production  of 
creatinin  (p.  138).  Hypoxanthin  is  oxidized  to  uric  acid  in  the 
muscle,  and  uric  acid,  if  carried  to  the  liver,  which  is  certainly 
the  principal  organ  for  its  destruction,  may  there  be  oxidized. 
Such  of  the  purin  bases  as  escape  oxidation  may  be  excreted 
by  the  blood  flowing  through  the  kidney,  even  as  uric  acid  is 
excreted  under  the  same  circumstances. 

Siven^  does  not  believe  that  muscular  work  appreciably 
raises  the  production  of  endogenous  purins.  He  thinks  that 
the  reduction  in  purin  elimination  during  the  night  time  is  due 
to  general  inactivity  of  all  the  tissues,  and  shows  that  when  an 
evening  meal  containing  much  protein  is  taken  and  the  kidney 
is  made  thereby  to  functionate  during  the  night,  then  the  purin 
elimination  is  increased.  Burian's  discovery  of  increased 
elimination  during  work  was  perhaps  due  to  the  fact  that  the 
work  was  accomplished  during  the  morning  hours,  when  an  in- 
creased elimination  due  to  purins  retained  during  the  night 
would  normally  occur. 

Mendel  and  Brown^  have  determined  the  hourly  excretion 
of  uric  acid  as  influenced  by  the  ingestion  of  meat,  liver,  and  other 
animal  tissues.  The  increase  in  the  eliminated  uric  acid  is 
very  marked  and  reaches  a  maximum  two  or  three  hours  after 
the  ingestion  of  these  animal  tissues.  Thus  after  the  ingestion 
of  600  grams  of  chopped  meat  the  uric  acid  elimination,  which 
had  been  19  milligrams,  rose  during  the  following  three  hourly 
periods  to  28,  88,  and  98  mifligrams  and  then  fell  in  successive 
hours  to  79,  73,  51,  36,  25,  and  22  milligrams.  It  wifl  be  seen 
later  that  such  curves  of  exogenous  uric  acid  excretion  do  not 
occur  in  the  gouty  patient  in  whom  there  is  uric  acid  retention 
(see  p.  354). 

Just  as  the  whole  trouble  in  diabetes  turns  upon  the  in- 

'  Siven:   Abstract  in  " Zentralblatt  fiir  Stoffwechsel,"  1906,  Bd.  i,  p.  81. 
^Mendel  and   Brown:  "Journal  of   the  American   Medical  Association," 
1907,  vol.  xlix,  p.  896. 


PURIN   METABOLISM. — GOUT.  351 

ability  of  the  organism  to  destroy  sugar,  so  the  symptoms  mani- 
fested in  gout  are  dependent  upon  the  deposit  of  acid  urate  of 
sodium  in  certain  localities.  One  of  the  earliest  descriptions  of 
gout  comes  from  Sydenham,  who  suffered  for  forty  j^ears  from 
the  disease  and  published  an  extended  account  of  it  in  1683. 
It  was  Garrod  ^  who  first  established  the  fact  that  uric  acid  was 
present  in  the  blood  of  gouty  persons.  He  believed  that  this  ex- 
cess of  urate  was  the  cause  of  gout,  the  excess  being  deposited 
from  the  blood  in  the  joints  in  the  form  of  crystals.  The  problem 
of  metabolism  in  gout  is  a  problem  of  the  factors  entering 
into  the  cause  of  this  deposit  of  urate.  The  general  metabolism, 
exclusive  of  the  purin  factor,  is  exactly  the  same  as  in  health. 
Magnus-Lev}^  proved  that  the  oxygen  absorption  and  carbon 
dioxid  elimination  is  the  same  in  gout  as  in  health.  The  cause 
of  the  trouble  must  be  sought  elsewhere  than  in  a  reduced 
general  oxidation  power  of  the  tissues. 

Clinical  experience  teaches  that  the  predisposing  causes  are 
excessive  eating,  little  muscular  exercise,  the  abuse  of  alcoholic 
beverages,  and  lead-poisoning. 

Beebe^  has  administered  alcohol  in  various  forms  to  a  normal 
individual.  He  finds  that  even  large  doses  have  no  effect  on  the 
hourly  excretion  of  uric  acid  in  a  fasting  man.  The  endogenous 
purin  metabolism  is  therefore  unchanged  by  the  ingestion  of 
alcohol.  It  is  important  to  know  that  alcohol  is  apparently 
without  effect  upon  such  part  of  the  purins  as  may  be  directly 
derived  from  cell  metabolism.  On  the  other  hand,  when 
Beebe  gave  alcohol  with  nuclein-containing  food,  the  uric  acid 
elimination  rose  markedly.  Further  investigation  of  this 
subject  by  Landau*  has  revealed  the  fact  that  the  influence  of 
alcohol  is  different  in  different  individuals,  and  that  usually 
there  is  a  slight  increase  in  the  output  of  endogenous  purins  after 

'  Garrod:    "The  Nature  and  Treatment  of  Gout,"  1859. 

*  Magnus-Levy :  "Berliner  klinische  Wochenschrift,"  1896,  ^o.  xix,  p.  416. 

*  Beebe:   "American  Journal  of  Physiology,"  1904,  vol.  xii,  p.  13. 

*  Landau:  "Dcutschcs  Archiv  fiir  klinische  Medizin,"  1909,  Bd.  xcv,  p.  280. 


352  SCIENCE   OF  NUTRITION. 

taking  alcohol.  Landau  also  found  that  there  was  always  a 
diminution  of  exogenous  purins  in  the  urine  as  a  result  of  alcohol 
ingestion.  Thus  while  48.4  per  cent,  of  hypoxanthin  given  in 
a  diet  free  from  purins  was  eliminated  in  the  urine  as  uric  acid 
on  a  normal  day,  only  38.2  per  cent,  was  excreted  as  uric  acid 
when  alcohol  was  added  to  the  diet.  This  is  interpreted  as 
indicating  that  alcohol  causes  a  retention  of  uric  acid  within 
the  organism. 

Pollack^  has  shown  that  in  chronic  alcoholics  the  retention 
of  ingested  purins  is  favored. 

Minkowski,^  with  a  master  hand,  summarizes  modern 
knowledge  concerning  gout  as  follows : 

1.  The  deposit  of  urate  in  the  tissues  is  the  first  change 
which  takes  place  in  the  formation  of  the  specific  gouty  nodules. 
These  tissues  are  not  necrotic,  as  taught  by  Ebstein. 

2.  The  tissue  changes  in  the  vicinity  of  the  gouty  nodules 
are  in  part  due  to  mechanical,  in  part  to  chemical  or  osmotic 
action,  caused  by  the  precipitated  urates. 

3.  The  acute  inflammation  in  gout,  as  observed  during  the 
attack,  is  produced  in  the  vicinity  of  the  urate  deposits  through 
some  unknown  cause.  Traumatic,  toxic,  or  infectious  elements 
appear  to  be  collectively  active  in  this  regard.  The  attack 
probably  constitutes  the  reaction  of  the  organism  to  rid  itself 
of  uric  acid,  an  effect  which  is  only  partly  realized. 

4.  An  accumulation  of  uric  acid  in  the  blood  is  a  constant 
accompaniment  of  gout. 

5.  The  increased  quantity  of  uric  acid  in  the  blood  must  not 
be  considered  as  the  cause  of  the  precipitation  of  urates  in  the 
gouty  nodules.  There  must  be  certain  local  influences  which 
favor  the  deposit  of  urates;  for  Klemperer  has  shown  that  the 
blood  of  gouty  patients  may  dissolve  much  more  uric  acid  than 
is  actually  present  in  it;   and  again,  the  blood  in  leukemia  may 

^  Pollack:   "Deutsches  Archiv  fiir  klin  Med.,"  1906,  Bd.  Ixxxviii,  p.  224. 
^Minkowski:    von  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1904, 
Bd.  ii,  p.  277. 


PURIN  METABOLISM. — GOUT. 


353 


contain  as  much  uric  acid  as  in  gout,  without  there  being  any 
indication  of  a  deposit  of  urate. 

6.  The  uric  acid  elimination  is  the  same  in  the  gouty  as  in 
the  normal  person,  except  at  the  time  of  the  attack.  Before 
the  attack  there  is  retention,  but  during  and  after  the  attack 
an  increased  excretion  of  uric  acid  in  the  urine. 

7.  The  accumulation  of  uric  acid  in  the  blood  is  not  due  to 
a  diminished  oxidation  of  uric  acid,  but  rather  to  a  diminution 
in  the  quantity  excreted  in  the  urine. 

8.  It  is  not  certain  that  the  lessened  excretion  of  uric  acid 
is  due  to  a  disturbance  of  renal  function.  Very  likely  it  depends 
upon  the  presence  of  uric  acid  in  some  abnormal  chemical 
union.  This  abnormal  substance  may  be  with  difficulty  elimi- 
nated in  the  urine,  but  may  lend  itself  readily  to  the  formation 
of  tophi  (p.  338). 

9.  The  ultimate  cause  of  the  unusual  behavior  of  uric  acid 
in  gout  is  probably  an  abnormal  metabolism  within  the  nuclei 
of  the  cells,  where  the  nucleic  acid  content  is  the  means  of  solu- 
tion and  conveyance  not  only  of  the  purin  bases  but  also  of 
uric  acid. 

The  opinions  of  other  modem  workers  vary  somewhat  from 
those  of  Minkowski,  as  appears  in  the  following: 

xAlmagia,^  in  Hofmeister's  laboratory,  has  performed  some 
interesting  experiments  and  concludes  that  the  older  view  of 
Garrod  is  correct, — that  is,  that  an  excess  of  urates  in  the  blood 
is  the  cause  of  gout.  Almagia  finds  that  thin  strips  of  cartilage 
suspended  in  dilute  neutral  solutions  of  sodium  urate  absorb 
the  salt,  do  not  destroy  it,  but  cause  it  to  be  deposited  in  fine 
crystals  within  the  cartilage.  He  furthermore  injected  five  to 
seven  grams  of  uric  acid  into  the  peritoneal  cavity  of  rabbits, 
a  dose  which  usually  killed  them.  On  testing  the  liver,  spleen, 
muscles,  and  lungs  with  the  murcxid  test  for  uric  acid,  negative 
results  were  obtained,  whereas  cartilage  gave  a  positive  reaction 
indicating  the   presence   of  urates.     Almagia  concludes   that 

1  Almagia:    "llofmeister's  Beitriigc,"  1905,  Bd.  vii,  p.  466. 
23 


354  SCIENCE   OF   NUTRITION. 

the  deposit  of  urates  in  the  cartilage  of  a  gouty  patient  is  but 
the  result  of  a  temporary  or  permanent  increase  in  the  uric  acid 
content  of  the  blood. 

Still,  in  leukemia,  where  there  must  be  a  large  destruction 
of  nucleoprotein,  as  evidenced  by  a  report  concerning  a  patient 
who  eliminated  12  grams  of  uric  acid  during  the  last  forty  hours 
of  life,  there  is  no  gout.^ 

Magnus-Levy,^  Vogt,^  and  Reach*  were  the  first  to  discover 
that  the  administration  of  glands  rich  in  nucleoprotein,  such  as 
thymus  and  pancreas,  to  gouty  persons,  did  not  cause  as  large 
an  excretion  of  uric  acid  in  the  urine  as  when  the  same  amounts 
of  these  materials  were  given  to  normal  individuals. 

The  work  of  Soetbeer^  is  of  the  best  modern  character,  and 
illustrates  the  retention  of  uric  acid  in  gout.  Soetbeer 
compared  the  excretion  of  uric  acid  by  gouty  people 
during  three-hour  intervals  with  that  of  normal  individuals, 
as  observed  by  Pfeil  (p.  349).  In  one  case  of  long- 
standing gout,  of  light  character  and  with  long  intervals 
between  the  attacks,  there  was  little  variation  from  the 
normal  in  the  uric  acid  excretion.  In  another  case  of  gout, 
a  patient  who  was  examined  between  the  attacks  showed  no 
increase  in  uric  acid  output  after  changing  from  a  purin-free 
diet  to  one  containing  320  grams  of  meat,  and  showed  only  a 
slight  increase  in  elimination  after  640  grams  of  meat  were 
given.  These  results  were  obtained  six  weeks  after  the  last 
attack  and  at  a  time  when  the  patient  was  entirely  free  from  pain. 
In  still  another  case  350  grams  of  meat  were  given  during  the 
attack  to  a  gouty  patient  who  had  no  fever  and  whose  urine  was 
free  from  albumin  and  sugar.     The  results  were  as  follows: 

^Magnus-Levy:    "Virchow's  Archiv,"  1898,  Bd.  clii,  p.  107. 
^Magnus-Levy:  "Zeitschr.  fur  klin.  Med.,"  1899,  Bd.  xxxvi,  p.  414. 
^  Vogt:  "Deutsches  Arch,  fiir  klin.  Med.,"  1901,  Bd.  Ixxi,  p.  21. 
*  Reach:  "Miinchener  med.  Wochenschr.,"   1902,  Bd.  xlix,  p.   1215.  ' 
^Soetbeer:    "Zeitschrift  f iir physiologische  Chemie,"  1904,  Bd.  xl,  p.  54. 


PURIN  METABOLISM. — GOUT.  355 

Uric  Acid 
IN  Gkaus. 

Diet  free  from  purins 0.276 

Diet  free  from  purins 0-328 

Diet  +  350  grams  meat 0.316 

"        "  "  "    0.270 

"    0.255 

In  this  experiment  even  during  the  days  of  purin-free  diet 
there  was  no  "morning  rise"  noted  as  a  normal  incident  by 
Pfeil.  The  hourly  uric  acid  excretion  was  very  even.  The 
kidney  was  apparently  removing  uric  acid  up  to  the  limit  of  its 
capacity. 

Linser^  tells  how  a  gouty  individual  suffering  from  eczema 
was  treated  with  the  Roentgen  rays.  Although  the  person  was 
on  a  purin-free  diet,  the  treatment  invariably  brought  on  an 
attack  of  gout,  on  account  of  the  increased  production  of  uric 
acid  within  the  body  which  normally  follows  such  treatment. 

Von  Noorden  and  Schliep^  suggest  that  gouty  patients  be 
tested  for  their  "tolerance"  for  purin  bodies  just  as  diabetics 
are  tested  for  their  tolerance  for  carbohydrates.  Four  hundred 
grams  of  meat  contain  0.24  gram  of  purin  nitrogen,  of  which  in 
the  normal  person  one-half  is  oxidized  and  one-half  eliminated 
in  the  urine — 0.24  gram  N  =  0.72  gram  uric  acid.  A  patient 
was  put  on  a  purin-diet  free;  was  given  400  grams  of  meat, 
then  put  on  a  purin-free  diet  again,  and  afterwards  was  tested 
with  200  grams  of  meat.     The  results  were  as  follows: 

Uric  Acid 
j)j^Y_  Diet.  in  Grams. 

4 Purin-free 0.462 

c  "  "    -|-  400  g.  meat 0.522 

6 "  "    +  400  g.  meat 0.544 

7  "  "    0.539 

8 "  "  °-528 

9 "  "   °-458 

10 "  "    4-  200  g.  meat 0.549 

„  "  "    -t-  200  g.  meat 0.655 

12.'.'.'.'.'. "        "   °-647 

I,  "        "   0.499 

14 - "        "   °-433 

»  Linscr:    "Therapie  der  Gcgenwart,"  1908,  No.  4. 

2  Von   Noorden   and   Schlicp:    "Berliner  klinische  Wochcnschrift,"    1905, 

Bd.  xlii,  p.  1297. 


356  SCIENCE   OF  NUTRITION. 

The  authors  conclude  that  while  the  increased  uric  acid 
output  after  giving  400  grams  of  meat  is  not  what  it  would  be 
normally,  yet  after  giving  200  grams  the  quantity  of  additional 
uric  acid  (which  should  amount  to  0.18  gram)  is  fully  elimi- 
nated. Hence  this  patient  had  a  tolerance  for  the  purins  in  200 
grams  of  meat. 

Dietetic  rules  for  gouty  sufferers  are  intended  to  combat 
the  fundamental  anomalies  of  the  metabolism.  The  organism 
must  not  be  overloaded  with  uric  acid.  Minkowski's  rules^ 
for  treatment  of  gout  may  be  thus  abstracted:  Sweetbreads, 
liver,  and  kidney  are  to  be  strictly  excluded  from  the  diet  since 
they  contain  purin  bases  in  large  quantity.  Meat  is  to  be 
taken  in  moderation  only.  Wine  should  be  taken  sparingly 
or  not  at  all,  and  beer  rigidly  excluded  on  account  of  the  nuclein 
in  yeast.  Cathartics  may  be  given  to  rid  the  intestine  of  purin 
bodies  excreted  into  the  intestinal  canal,  and  water-drinking, 
which  promotes  a  larger  flow  of  urine  and  increased  uric  acid 
elimination,  is  strongly  to  be  commended.  The  diet  for  a 
gouty  patient  should  contain  each  day  100  or  120  grams  of 
protein,  80  or  100  grams  of  fat,  and  250  or  300  grams  of  car- 
bohydrates (2200  to  2600  calories).  This  should  not  include 
more  than  from  200  to  250  grams  of  meat  per  day.  Indigestible 
cakes,  pies,  rich  foods,  and  heavy  salads  should  be  forbidden. 
Moderation  and  self-control  are  the  watchwords  for  the  gouty 
sufferer. 

It  is  impossible  to  increase  the  oxidation  of  uric  acid,  and 
no  treatment  now  known  increases  its  solubility.  Minkowski 
hopes  that  some  organic  compound  may  be  discovered  which 
will  accomplish  this  purpose.  He  believes  the  relief  given  by 
preparations  of  the  salicylate  group  is  afforded  only  through 
their  stopping  pain  and  promoting  perspiration. 

Bearing  the  facts  of  the  above  discussion  in  mind,  the 
reader  will  comprehend  that  present-day  doctrines  concerning 
metabolism  in  gout  may  shortly  become  entirely  obsolete 
through  new  and  far-reaching  discoveries. 

^  Minkowski:  "Deutsche  medizinische  Wochenschrift,"  1905,  Bd.  xxxi,  p.  409. 


CHAPTER  XV. 
THEORY  OF  METABOLISM. 

There  has  been  a  difference  of  opinion  as  to  whether  the  food 
substances  must  iirst  become  vital  integrants  of  the  Hving  cell,  or 
whether  the  non-living  food  materials  are  metabolized  without 
ever  becoming  a  constituent  part  of  the  living  protoplasm. 

Pfliiger  held  the  former  view, — that  incorporation  of  nutri- 
tive matter  with  the  living  substance  is  essential  to  its  metab- 
olism. He  conceived  that  living  protein  may  contain  the  labile 
cyanogen  group  in  contrast  with  dead  protein  which  contains 
the  amino  group.  He  illustrated  this  by  Wohler's  classic 
experiment  of  the  easy  conversion  of  ammonium  cyanate  into 
urea: 

NH.OCN  =  (H2N)2CO 

Voit's  theory  was  that  the  living  protein  is  comparatively 
stable  and  that  food  protein  which  becomes  the  circulating  pro- 
tein of  the  blood  is  carried  to  the  cells  and  promptly  metabolized. 
The  other  foodstuffs  are  also  burned  without  first  entering  into 
the  composition  of  the  cell. 

A  mass  of  living  cells  composing  the  substance  of  a  warm- 
blooded animal  has  the  same  requirement  of  energy  as  any 
similar  mass  of  living  cells  composing  the  substance  of  any  other 
animal  of  the  same  size  and  shape. 

The  uniformity  of  the  energy  requirement  is  illustrated  by 
the  fact  that  the  number  of  calories  given  off  during  the  twenty- 
four  hours  by  one  square  meter  of  surface,  in  various  animals 
and  in  man  in  the  condition  of  starvation,  is  the  same. 

Even  in  pathological  conditions  a  remarkable  constancy  of 
total  heat  production  is  apparent.    Thus,  in  such  typical  dis- 

.357 


358  SCIENCE    OF   NUTRITION. 

turbances  as  anemia,  diabetes,  gout,  and  obesity,  the  general 
laws  governing  the  output  of  carbon  dioxid,  the  absorption  of 
oxygen,  and  the  production  of  heat  are  found  to  be  the  same  as 
in  health.  Also  after  castration  the  metabolism  is  unchanged, 
except  as  it  may  be  influenced  by  increased  indolence.  In 
fever  the  metabolism  and  heat  production  increase,  and  this  to 
a  large  extent  on  account  of  the  warming  of  the  cells.  In 
exophthalmic  goiter  there  is  certainly  an  increase  in  metabolism, 
due  to  the  stimulus  of  an  excessive  production  of  iodothyrin  in 
the  thyroid  gland,  while  in  myxedema  the  absence  of  the  same 
substance  causes  a  considerable  reduction  in  the  metabolism. 
These  changes  are  probably  due  to  alterations  in  the  irritability 
of  the  nervous  system.  Drugs  may  influence  the  course  of 
metabolism,  iodothyrin  increasing  it  and  morphin  profoundly 
diminishing  it,  but  on  the  whole  the  most  striking  fact  is  not  the 
variability,  but  rather  the  uniformity,  of  the  processes  con- 
cerned in  the  maintenance  of  life. 

Within  recent  years  the  work  of  Kossel,  Fischer,  Hofmeister, 
Osborne,  Abderhalden  and  Levene  has  given  a  more  definite  con- 
ception of  the  composition  of  protein  than  was  before  possible. 
There  is  every  indication  that  the  protein  molecule  consists 
fundamentally  of  groups  of  amino-fatty  acids  banded  together. 
Proteins  vary  with  the  integral  components  of  their  chemical 
chains.  It  has  long  been  known  that  the  end-products  of 
tryptic  digestion  include  such  substances,  but  Kutscher  first 
showed  that  continued  tryptic  digestion  resulted  in  the  almost 
complete  transformation  of  protein  into  these  amino-acids. 
Cohnheim  discovered  erepsin,  an  enzyme  derived  from  the  in- 
testinal wall,  which  rapidly  converts  albumoses  into  these 
substances. 

Protein  metabolism  in  plants  and  animals  occurs  in  striking 
similarity  to  the  changes  brought  about  by  enzymes  and  hy- 
drolytic  agents  acting  on  protein  outside  of  the  tissues.  Thus 
in  the  germinating  seed  Schultze^  finds  that  asparagin,  leucin, 

^  Schultze  and  Castoro:  "Zeitschr.  f.  physiol.  Chemie,"  1904,  Bd.  xliii,  p.  170. 


THEORY  OF   METABOLISM.  359 

tyrosin,  histidin,  arginin,  and  lysin  arise  from  the  metabolism 
of  protein. 

All  forms  of  protein  decomposition  follow,  therefore,  the 
pathway  of  cleavage  into  amino-acids.  This  all  indicates  a 
wonderful  biological  kinship. 

The  metabolic  history  of  many  of  these  substances  has 
already  been  set  forth  in  the  preceding  chapters,  and  it  is  here 
imnecessary  to  recapitulate. 

The  quantity  of  the  combustion  depends  on  the  power  of  the 
cells  to  metabolize  (Voit).  In  the  resting  state  this  metabolic 
power  of  the  cells  is  influenced  by  the  "law  of  skin  area"  (Rub- 
ner).  Temperature  (cooling  or  warming)  and  nerve  excitation 
(muscle  work,  chemical  regulation)  affect  the  power  of  the  cells 
to  metabolize,  perhaps  through  a  variation  in  the  capability  of 
oscillation  of  the  particles,  an  effect  which  is  in  turn  maintained 
at  the  expense  of  the  energy  derived  from  metabolism.  Living 
protoplasm  metabolizes  in  accord  with  its  necessities  at  the 
time,  and  never  more.  A  large  supply  of  nutrient  materials 
will  not  increase  cell  metabolism.  If  food  be  ingested 
above  the  requirement  for  the  organism,  any  excess  will  be 
retained  in  the  body  (unless  it  has  passed  out  undigested). 
The  kind  of  metabolism  depends  upon  the  constitution  of  the 
fluid  feeding  the  cells,  whether  proteins,  carbohydrates,  or  fats 
have  been  ingested.  The  reason  for  the  metabolism  lies  un- 
known within  the  cells.  Liebig  conceived  the  cause  to  be  the 
swinging  motion  of  the  small  constituent  particles  of  the  cells 
themsch'es. 

Rubner^  gives  the  followmg  theory  of  metabolism.  The 
nature  of  the  processes  which  take  place  in  living  protoplasm  is 
not  known.  High-sounding  names  which  have  been  used  in 
this  connection  are  only  a  cloak  for  ignorance.  The  col- 
loidal condition  of  the  protoplasm  of  the  cells  in  both  warm  and 
cold  blooded  animals  is  nearly  identical.  All  cells,  however,  are 
not  similar  in  constitution,  since  some  bacteria  are  killed  at 

'  Rubner:    "Archiv  fur  Hygiene,"  1908,  Bd.  Ixvi,  p.  15. 


360  SCIENCE    OF   NUTRITION. 

30°  while  others  thrive  at  60°.  This  latter  variety  must  synthe- 
size proteins  which  are  not  coagulable  at  the  higher  temperature. 
One  may  imagine  the  mechanism  of  the  energy  metabolism  to 
be  somewhat  as  follows.  The  whole  mass  of  the  protoplasm 
cannot  be  continually  employed  in  the  production  of  energy  but 
only  certain  parts  of  it.  These  parts,  by  virtue  of  the  charac- 
teristic vibration  of  their  molecules,  possess  the  power  to  at- 
tract and  break  up  contiguous  food  radicles.  Such  affinities 
must  be  specific.  It  is  necessary  to  consider  two  fundamental 
types  of  cell  affinities:  (i)  for  carbohydrates  and  (2)  for  fat — 
neglecting  those  for  alcohol,  glycerin,  etc.  One  is  led  to  this 
because  it  is  known  that  in  diabetes  the  affinity  for  carbohydrate 
is  lost  while  that  for  fat  remains.  Wlien  the  necessity  for  in- 
creased mechanical  effect  arises,  the  amplitude  of  the  vibrations, 
or,  in  other  words,  the  strength  of  the  affinities,  is  increased  by 
means  of  nerve  stimuli.  It  is  immaterial  to  the  life  of  proto- 
plasm which  of  the  two  affinities  is  used.  If  the  carbohydrate 
type  of  cell  affinity  is  active,  that  for  fat  becomes  inactive  and  vice 
versa.  If  the  carbohydrate  type  is  annihilated,  as  in  diabetes, 
then  the  fat  type  may  alone  provide  for  the  energy  production. 
The  affinities  of  the  vibrating  molecules  may  be  considered  as 
acting  somewhat  in  the  same  way  as  enzymes,  but  this  similarity 
is  limited  to  the  primary  attack  upon  the  food  radicles.  The 
approach  of  the  nutrient  radicles  within  the  range  of  the  affinities 
is  accompanied  by  atomic  changes  in  the  food  particles  and 
possibly  by  the  immediate  entrance  of  oxygen.  How  the  oxygen 
enters  into  the  complex  is  not  definitely  known,  but  the  im- 
portant consideration  relates  to  the  liberation  of  energy.  The 
sequence  of  the  atomic  changes  and  the  entrance  of  oxygen  must 
be  so  ordered  that  at  the  moment  of  the  breaking  up  the  nutrient 
radicles,  mechanical  work  is  accomplished  upon  the  living 
protoplasm,  work  which  can  be  expended  upon  neighboring 
parts  of  the  protoplasm  and  which  for  the  time  renders  the 
affinities  inactive.  It  is  entirely  a  matter  of  indifference  whether 
the  result  is  obtained  from  carbohydrate  or  from  fat,  for  the  law 


THEORY  OF  METABOLISM.  36 1 

of  isodynamic  equivalents  asserts  that  the  requirement  of  energy- 
may  be  satisfied  either  by  carbohydrates  or  by  fat.  The  living 
protoplasm  acquires  energy  at  the  moment  of  the  break-down 
of  the  foodstuffs.  This  acquired  swinging  motion  of  the  mole- 
cules gradually  subsides  with  the  evolution  of  heat,  and  the 
original  condition  in  which  the  afifinities  were  active  returns  and 
again  more  food  radicles  are  attacked.  This  theory  of  metab- 
olism represents  Rubner's  idea  of  the  method  by  which  the 
energy  of  the  food  is  transmitted  to  the  living  protoplasm  in 
response  to  the  demand  for  energ}'  for  the  maintenance  of  life. 
Besides  this  a  number  of  cleavages  and  other  changes  in  chem- 
ical constitution  occur  which  also  either  evolve  or  absorb  heat. 
These  are  purely  thermo-chemical  processes  and  do  not  fur- 
nish the  body  with  energy  in  the  sense  just  described. 

Each  ingested  foodstuff  exerts  a  specific  dynamic  action 
(Rubner).  At  a  temperature  of  ;^^°  the  ingestion  of  the  starva- 
tion requirement  of  energy  in  the  form  of  fat  increases  the  re- 
quirement for  energ}'  lo  per  cent.,  carbohydrate  raises  it  5  per 
cent.,  protein  30  per  cent.  In  other  words,  in  the  case  of  meat, 
in  order  to  obtain  calorific  equilibrium  about  140  calories  must 
be  ingested  instead  of  loo,  if  that  represents  the  starvation  re- 
quirement. Rubner^  explains  that  the  cells  of  the  body  do  not 
require  more  energy  after  meat  ingestion  than  in  starvation, 
but  that  the  heat  produced  by  a  preliminary  cleavage  of  protein 
into  dextrose  on  the  one  hand,  and  into  a  nitrogen-containing  rest 
on  the  other,  while  yielding  heat  to  the  body  does  not  furnish  the 
actual  energy  for  the  vital  activities  of  the  protoplasm.  This 
is  furnished  principally  by  the  dextrose  derived  from  the  protein. 
Although  it  is  necessary  to  abandon  the  older  theory  which 
pronounces  glycogen  (or  dextrose)  a  direct  cleavage  product  of 
protein,  still  the  explanation  of  Rubner  remains  tenable  if  inter- 
preted in  a  newer  light.  If  the  energy  requirement  of  the 
cell  remains  constant  at  100,  even  after  the  ingestion  of  140 
calories  of  protein,  then  71.4  per  cent,  of  the  total  heat  value  of 
the  protein  is  the  quantity  actually  used  for  the  vital  processes. 
'  Rubner:   "Gcsetze  des  Energieverbrauchs,"  1902,  p.  380. 


362  SCIENCE    OF    NUTRITION. 

Since  it  has  been  shown  in  the  writer's  laboratory  that  meat 
protein  yields  58  per  cent,  of  dextrose  in  metabolism,  it  may  be 
calculated  that  52.5  per  cent,  of  the  total  energy  of  protein  may  be 
available  for  the  cells  in  the  form  of  sugar.  A  balance  of  19 
per  cent,  must  be  obtained  from  other  compounds,  while  28.5 
per  cent,  of  the  total  heat  value  is  wasted  as  heat  without  ever 
having  been  brought  into  the  service  of  the  life  processes  of  the 
cells.     (Seep.  163.) 

The  constancy  of  the  energy  requirement  in  metabolism 
makes  difficult  the  explanation  of  the  action  of  the  various  fer- 
ments found  in  the  body.  These  are  of  three  varieties :  hydro- 
lytic,  synthetic,  and  oxidizing,  but  these,  from  the  very  principles 
of  our  knowledge,  must  be  subservient  to  the  requirement  of  the 
living  cells,  and  not  themselves  masters  of  the  situation,  as, 
for  example,  they  become  in  the  autolysis  of  dead  tissue.  It 
seems  to  be  the  requirement  of  the  mechanism  of  cell  activity 
which  determines  metabolism,  and  not  primarily  the  action  of 
enzymes,  whose  influence  appears  to  be  only  intermediary. 

FriedenthaP  shows  that  protein,  colloidal  carbohydrates, 
fats,  and  soaps  are  not  oxidizable  in  the  cellular  fluids  without 
previous  hydrolytic  cleavage.  After  hydrolysis,  however,  the 
oxidases  may  effect  an  oxidation  of  the  smaller  molecules.  The 
necessity  of  the  hydrolytic  ferment  is  also  seen  in  the  non- 
combustion  of  dextrose  after  the  extirpation  of  the  pancreas,  the 
organ  by  which  the  ferment  is  supplied.  Oxygen  and  the 
oxidases  are  present  in  ample  quantity,  but  the  sugar  is  not 
burned  unless  it  be  broken  by  its  specific  ferment.  In  the  mean- 
time the  cell  avails  itself  of  a  compensatory  energy  supply  from 
other  sources.  Metabolism  depends  therefore  upon  a  definite 
law  of  utilization  of  energy  equivalents. 

However  clearly  formulated  the  laws  of  metabolism  may  be, 
and  many  of  them  are  as  fixed  and  definite  as  are  any  laws  of 
physics  and  chemistry,  still  the  primary  cause  of  metabolism 
remains  a  hidden  secret  of  the  living  bioplasm. 

^Friedenthal:  Verhandlungen  der  Berliner  physiologischen  Gesellschaft, 
"Archiv  fur  Physiologic,"  1904,  p.  371. 


APPENDIX. 


Fig.   13. — Thermometer  showing  comparison  of  Fahrenheit  and  Centigrade 

scales. 

3(>3 


3^4 


SCIENCE    OE  NUTRITION. 


CONVENIENT   COMPARISONS   OF  METRIC  AND  AVOIRDUPOIS 

WEIGHTS. 

I  kilogram        =       2.2046  pounds 

I  pound  =  453-6        grams 

I  ounce  =  28.3        grams 

I  liter  =  61.027    cubic  inches  =  1.7608  pints 

I  gram-calorie  =       0.425  kilogram-meters  of  mechanical  energy. 


THE  CHEMICAL  COMPOSITION  OF  NORMAL  URINES  ON  PURIN- 
FREE  DIETS.     (After  FoHn,  see  p.  138.) 


Person. 


E.  S.  A. 


June. 


29th        30th 


H.  B.  H. 


]SIarch. 


July. 


8th  pth         10th    !     13th        20th 


Total  N  in  grams 14.6 

Urea  N 12.6 

0.54 
0-39 
0.15 
0.96 


Ammonia  N 

Creatinin  N 

Uric  Acid  N 

Undetermined  N. 


Total  SO3  in  grams 3.02 

Inorganic  SO3 \  2.56 

Ethereal  SO3 |  0.26 

Neutral  SO, \  0.20 


In  per  cent,  of  total  N: 

UreaN 

Ammonia  N 

Creatinin  N 

Uric  Acid  N 

Undetermined  N 


In  per  cent,  of  total  SO3 

Inorganic  SO3 

Ethereal  SO, 


86.0 
3-6 
2.7 
i.o 
6.6 


H-7 
8.6 


Neutral  SO3 1    6.7 


15.8 
13-9 
0.54 
0.43 
o.ii 


2.94 
2.58 
0.22 
0.14 


87.7 

3-3 
2.7 
0.7 
5-6 


87.7 

7-4 
4.9 


15-9 

13-5 
0.41 
0.70 
0.26 
1.06 

3-03 
2.48 
0.20 
0-35 


64.7 
2.6 
4.4 
1.6 
6.7 


6.6 
11.6 


15-5 
13-4 
0.41 
0.64 
0.23 
0.79 

2.49 
2.05 
0.18 
0.26 


86.4 
2.7 
4.1 
1-7 

5-1 

82.0 

7.2 

10.8 


15.0 
12.9 

0.43 
0.69 
0.27 


2.19 

1-74 
0.19 
0.26 


86.2 


16.8 

14.7 
0.49 
0.58 
0.18 
0.85 


79-4 
8.6 


3-6 

2.2 

0.42 

0.60 

0.09 

0.27 


3.64  I  0.76 

3.27  I  0.46 

0.19  o.io 

0.18  0.20 


87.5  !  61.7 

2.9     ,    3.0  11.3 

4.6     j    3.6  17.2 

1.8         1.05  2.5 

4-4         4-85  7-3 


90.0  j  60.5 
5.2  13.2 
4.8     ,  26.5 


TABLE  SHOWING  THE  COST  OF  PROTEIN  AND  ENERGY 

As  Fdrnished  by  a  Number  of  Common  Food  Materials,  at  Prices  Current  in   the 
Eastern  Part  of  the  United  States. 

Compiled  by  Langworthy,  U.  S.  Department  of  Agriculture,  1905,  in  Farmers'  Bulletin, 

No.  8s,  p.  19. 

(i  pound  =  453.6  grams.) 


Kind  of  Food  Material. 


Codfish,  whole,  fresh 

Codfish,  steaks 

Bluefish 

Halibut 

Codfish,  salt 

Mackeral,  salt 

Salmon,  canned 

Oysters  (solids,  30  cents  quart). 
Oysters  (solids,  60  cents  quart). 

Lobster 

Beef,  sirloin  steak 

Beef,  sirloin  steak 

Beef,  round 

Beef,  stew  meat 

Beef,  dried,  chipped 

Mutton  chops,  loin 

Mutton,  leg 

Pork,  roast,  loin 

Pork,  smoked  ham 

Milk  (7  cents  quart) 

Milk  (6  cents  quart) 

Wheat  flour ■ 

Corn  meal 

Potatoes  (90  cents  bushel) 

Potatoes  (45  cents  bushel) 

Cabbage 

Com,  canned '. 

Apples 

Bananas 

Strawberries 


PL,   Z 


Cents. 


15 
30 
18 

25 
20 

14 

5 
25 


3 
3 
3 
2 

i 

A 
10 
li 

7 
7 


Dollars. 
0.90 

71 
1.20 
1. 18 

•44 

.61 

.62 

2.50 

5.00 

3-05 

1.52 

1. 21 

•74 

•38 

•95 

1.48 

1.46 

.90 

1-55 

1.06 

.91 

.26 

.22 

.83 

.42 

1.79 

3^57 
5.00 

8-75 
7.78 


Amounts  for  10  Cents. 


US 

5  " 
0  Z 

t^  m 

?=.°  £ 

z 

0  w 

ri*" 

u 

H 

H  0»-l 

0 

0 

0       ^ 

PS 

U 

H 

Ph 

Cents. 

Lbs. 

Lb. 

48 

1.000 

0.1  II 

36 

•833 

.142 

58 

•833 

.083 

40 

•556 

.085 

23 

1.429 

.229 

10 

1. 000 

.163 

18 

■833 

.162 

68 

.667 

.040 

i,,6 

•333 

.020 

129 

•556 

•033 

26 

.400 

.066 

21 

.500 

.083 

16 

.714 

.136 

S 

2.000 

.266 

33 

.400 

.106 

14 

.500 

.068 

2S 

•454 

.069 

10 

.833 

.112 

14 

•454 

.064 

II 

2.857 

.094 

10 

3-3i^ 

.110 

2 

3-333 

.380 

I 

fJ.OOO 

.460 

5 

6.667 

.120 

2 

13-333 

.240 

21 

4.000 

.056 

23 

1. 000 

.028 

7 

6.667 

.020 

24 

T.429 

.Oil 

42 

r.429 

.013 

Calories. 
209 
274 
172 
253 
437 
998 

547 

147 

74 

77 

380 

475 

615 

1,862 

3,03 
694 

394 
1,016 

729 

891 

1,040 

5.363 
8,05  s 
2,020 
4,040 
484 

444 

1,420 

414 

240 


365 


366 


SCIENCE   OF  NUTRITION. 


A  more  extensive  compilation  which  permits  not  only 
the  calculation  of  the  nutritive  value  of  the  particular  edible 
food  but  also  of  the  approximate  weight  of  inedible  waste  en- 
tailed in  the  direct  purchase  of  the  material  in  the  market, 
is  as  follows : 


COMPOSITION   OF  ORDINARY  FOOD   MATERIALS 

According  to  Atwater  and  Bryant. 
Report  of  the  Storrs  Agricultural  Experiment  Station,  1899,  p.  113,  somewhat  abridged. 


Kind  of  Food  Material. 


Animal  Foods. 
Beef  {fresh). 

Brisket 

Chuck 

Flank 

Loin,  lean 

Loin,  medium 

Loin,  fat 

Neck 

Plate 

Ribs 

Roiind,  lean 

Round,  medium 

Round,  fat 

Round,  second  cut 

Rump 

Fore  shank 

Tongue 

Shoulder  and  clod 

Fore  quarter 

Hind  quarter 

Side,  lean 

Side,  medium 

Side,  fat 

Liver 

Suet  (unrendered  tallow) 
Hind  Shank 

Beef   {preserved   and 
cooked). 

Dried  and  smoked 

Brisket,  corned 

Flank,  corned 


Edible  Portion. 

35 

_o 

Available  Nutrients. 

(S-o 

0  "^ 

^a 

A  « 

3.  A'°.M 

iS-o 

u 

p-'B 

a 

•Sl 

It^, 

s 

^ 

1^ 

2 

^.5 

< 

|-,|0 

% 

% 

% 

% 

% 

% 

% 

Calo- 
ries. 

23-3 

54-6 

2.1 

iS-3 

27.1 

•7 

147s 

ib.3 

62.7 

1.8 

17.9 

17.I 

7 

1095 

10.2 

60.2 

1.9 

18.3 

19.9 

7 

1225 

I3-I 

67.0 

1.2 

19.1 

12. 1 

I 

0 

900 

13-3 

60.6 

1.8 

17.9 

19.2 

8 

1185 

10.2 

54-7 

1.9 

17.0 

26.2 

9 

1470 

27.6 

63-4 

1.6 

19-5 

15-7 

7 

1065 

ib.5 

54-4 

2.2 

16.0 

27.6 

6 

1510 

20.8 

55-5 

2.0 

17.0 

25-3 

7 

1430 

8.1 

70.0 

I.O 

20.7 

7-5 

I 

I 

735 

7.2 

GS-5 

1.6 

19.7 

12.9 

8 

950 

12.0 

60.4 

1.6 

18.9 

18.5 

I 

0 

117s 

19-5 

69.8 

1-3 

19.8 

8.2 

8 

750 

20.7 

5<3.7 

2.0 

16.9 

24.2 

7 

1380 

36-9 

67.9 

1.4 

19.8 

II. 0 

7 

86q 

2b.5 

70.8 

1-3 

18.3 

8.7 

8 

740 

16.4 

b8.3 

1-5 

19.0 

10.7 

8 

840 

18.7 

60.4 

1.8 

17.4 

20.3 

7 

1220 

15-7 

59-« 

1.8  . 

17.8 

20.5 

7 

1240 

19-5 

67.2 

1-3 

18.7 

12.5 

9 

910 

17.4 

59-7 

1.8 

17.6 

20.9 

7 

1250 

13.2 

47-8 

2-5 

15-7 

34-6 

.S 

1805 

7.0 

71.2 

1.2 

20.4 

4-3 

1-7 

I 

2 

620 

13-7 

4-3 

4.6 

77-7 

2 

3440 

53-9 

67.8 

1.4 

20.3 

10.9 

7 

87s 

4-7 

54-3 

3-5 

29.1 

6.2 

6.8 

850 

21.4 

50-9 

3-2 

17.8 

23-5 

.. 

4.2 

1370 

12. 1 

49.9 

2.7 

14.2 

31-4 

•  • 

2 

2 

1635 

APPENDIX. 


367 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


3.2 


Edible  Portion. 


Animal  Foqds. 

(Beef,  preserved  and 

cooked). 

Plate,  corned 

Rump,  corned 

Canned,  boiled 

Canned,  corned 

Boiled  beef  (cut  not  given) 

Roast,  cooked 

Loin  steak,  cooked 

Tripe,  pickled 


Veal  (jresh). 


Breast 

Chuck 

Cutlets  (round). 

Flank 

Leg 

Loin 

Neck 

Rib 

Shank 

Fore  quarter. . . 
Hind  quarter. . . 

Side 

Liver 


14-5 
6.0 


21.3 

18.9 

3-4 

14.2 
16.5 
31-5 
24-3 
62.7 

24-5 

20.7 

22.6 


Lamb  (fresh). 

Breast  or  chuck 19. i 

Leg 17.4 

Loin 14.8 

Neck 17.7 

Shoulder 20.3 

Fore  quarter 18.8 

Hind  quarter 15.7 

Side I  19.3 


Lamb  (cooked). 

Chops,  broiled !  13.5 

Leg,  roast I     . . 

Mutton  (fresh). 

Chuck 21.3 

Flank 9.9 


% 


40.1 
58.1 
51.8 
51-8 
38.1 
48.2 
54-8 
86.5 


66.0 

73-0 
70.7 
68.9 
70.0 
69.0 
72.6 
72.7 

74-5 
71.7 
70.9 
71-3 
73-0 


56.2 
639 
53-1 
567 
51-8 

55-1 
60.9 
58.2 


47.6 
67.1 


50-9 
46.2 


Available  Nutrients. 


% 


3-7 
2.2 
2.2 
2.7 
2.7 
2.4 
2.0 
.6 


1-5 
I.I 

1-3 
1-3 
1-3 
1-3 
I.I 
1.2 
i.o 
1.2 
1.2 
1.2 
•9 


2.0 

1-7 
2.2 
1.9 
2.2 
2.0 
1.8 
2.0 


2-S 
1.4 


2.4 
2.6 


13-3 
14.8 
24.7 

25-5 
25-4 
21.6 
22.8 
"•3 


18.9 
19.1 
19.7 
19.9 
19.6 

19-3 
19.7 


19.4 

20.1 

19.6 

9-7 


18.S 
18.6 
18.1 
17.2 
17.6 
17.8 
19.0 
17.1 


21.0 
19.1 

14.6 
14.7 


39-« 
22.1 
21.4 
17.8 
33-2 
27.2 
19.4 
I.I 


13-3 
6.2 

7-3 
9.9 
8.6 
10.3 
6.6 
5-8 
4.4 
7.6 
7-9 
7-7 
5-0 


22.4 

15-7 
26.9 
2-5.6 
28.2 

24-5 
18.1 
21.9 


28.4 
12. 1 


3 1 -9 
36.4 


% 


."£ 


/o 

Calo- 

nes. 

•5 

1980 

.8 

1250 

.0 

14 1. S 

.0 

127s 

■7 

1930 

.0 

1410 

•9 

1290 

.2 

275 

.8 

950 

.8 

650 

.8 

710 

.8 

82s 

■9 

760 

.8 

830 

.8 

680 

.8 

650 

.8 

590 

•7 

715 

.8 

740 

.8 

725 

1.0 

410 

.8 

1335 

.8 

1050 

.8 

1520 

.8 

1360 

.8 

1565 

.8 

1410 

.8 

1 1 60 

.8 

1285 

1.0 

1640 

.6 

905 

•7 

i66t; 

•5 

i860 

368 


SCIENCE   OF   NUTRITION. 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


Animal  Foods. 

Mutton  (Jresh) 

Leg 

Loin 

Neck 

Shoulder 

Fore  quarter 

Hind  quarter 

Side 


Mutton  {cooked  and 
canned). 

Leg,  roast 

Corned,  canned 

Tongue,  canned 

Pork  (fresh). 
Chuck,  ribs  and  shoulder. 

Flank 

Loin,  chops 

Ham 

Shoulder 

Side 


Pork  {pickled,  salted  and 
smoked). 

Bacon 

Ham 

Shoulder 

Salt,  lean  ends 

Salt,  fat 

Pigs'  feet,  pickled 

Pork  {cooked). 

Ribs,  cooked , 

Steak,  cooked 

Sausage. 

Bologna 

Frankfort 

Pork 


f^-- 


Pi  XI 


Edible  Portion. 


% 

18.4 
16.0 
27.4 
22.5 
21.2 
17.2 


18.0 
19.7 
10.7 
12.4 

II-5 


7-7 
13.6 
18.2 


35-5 


Poultry  and  game  {fresh). 

Chicken,  broilers 

Fowl 

Goose 

Turkey 


3-3 


41.6 

2S-9 
17.6 
22.7 


% 
62.8 
50.2 
58.1 
61.9 

52-9 

54-8 

54-2 


50-9 
45-8 
47.6 


59-0 

52.0 

53-9 
51.2 

34-4 


18.8 
40.3 
45 -o 
19.9 

7-9 


33-6 
33-2 


60.0 
57-2 
39-8 


74.8 

63-7 
46.7 

55-5 


Available  Nutrients. 


% 

1-7 
2.4 
2.0 

1-7 
2.2 
2.1 
2.1 


3-0 
3-1 


2-3 

1.9 
2.2 
2.1 

2-3 

3-2 


4.8 

3-6 
3-8 
5-1 
S-4 
1.4 


3-1 
3-3 


2.4 

2-3 

3-1 


i.o 
1.6 

2-S 
1.9 


% 
17.9 

1-55 
16.4 
17.2 

I5-I 
16.2 

15-8 


24-3 
27.9 

23-7 


16.8 
17.9 
16.1 
14.8 
12.9 


9.6 
15.8 
15-4 


15.8 


24.1 
19-3 


19.0 
12.6 


20.9 
18.7 
15.8 
20.5 


% 
17. 1 
31-4 
23-4 
18.9 
29.4 
26.7 
27-5 


21-5 

21.7 
22.8 


29-5 
21. 1 
28.6 
27-5 
32-5 
52-5 


36-9 
30-9 
63-7 
81.9 
14.1 


35-7 
43-1 


16.7 
17.7 
42.0 


2.4 

iS-S 
34-4 
21.8 


o  ii 

6'^ 


% 


0-3 
I.I 
I.I 


% 


•9 
3-2 
3-6 


3-3 
3-6 
S-o 
4-3 
2.9 

•7 


1-7 


2.8 
2.6 
1-7 


3   0.11  O 

fa     " 


Calo- 
ries. 

1095 
1660 

1335 
1 160 

1570 
1475 
1500 


1410 
1495 
I04S 


1605 
1265 

I5SS 
1480 
1660 
2440 


2950 

1905 
1640 
2905 

3565 
920 


2020 
2245 

1085 
1 160 
2080 


520 
.»  I  1040 
.6  1800 
.8  I  8S3 


APPENDIX. 


369 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


10.4 


Animal  Foods. 

Poultry  and  game  {cooked 

and  canned). 

Capon 

Turkey,  roast 

Plover,  roast,  canned 

Quail,  canned 


Fish  (fresh). 

Bass,  black,  whole '  54. S 

Bluefish 48.6 

Codfish,  dressed 29.9 

Cod  steaks 9.2 

Flounder,  whole 61.5 

Haddock 51.0 

Halibut  steak i7-7 

Lake  trout I  48.5 

Mackerel I  44.7 

Weakfish 51 -9 

Whitefish,  whole 53.5 


41.9 

67-5 
81.4 


Shell  fish  (fresh). 

Long  clams,  in  shell 

Round  clams,  in  shell 

Oysters,  in  shell 

Oysters,  solids 

Clams,  round,  solids '     . . 

Crabs,  hard  shells 52.4 

Lobster 61.7 

Fish  (preserved  and 
canned). 

Cod,  salt 24.9 

Cod,  salt,  boneless I    1.6 

Halibut,  smoked 7.0 

Herring,  smoked 44.4 

Mackeral,  salt,  dressed 19.7 

Salmon,  cannefl 14.2 

Sardines,  canned 1    5.0 

Lobster,  canned ■. 

Clams,  canned 

Oysters,  canned 


Edible  Portion. 


59-9 
67-5 
57-7 
66.9 


76.7 
78.5 
58.5 
79-7 
84.2 
81.7 

75-4 
70.8 

73-4 
79.0 
69.8 


85.8 
86.2 
86.9 
88.3 
80.8 
77.1 
79.2 


535 
5S-0 
49.4 
34-6 
43-4 
63-5 
52-3 
77.8 
82.9 
834 


1-7 
1-3 
1-7 
1.6 


i.o 

i.o 

•5 

•9 

•7 

.8 

I.I 

1-3 

1-3 

■9 

1.4 


1.0 

•9 

.8 

.6 

1.0 

1.4 

I.I 


6.8 
5-5 
5-0 
5-2 
5-0 
1.9 

3-1 
1-3 
1.0 


Available  Nutrients. 


26.2 
17.1 
21.7 
21. 1 


20.0 
18.8 
10.8 
18.1 
13.8 
16.7 
18.0 

17-3 
18.1 

17-3 


8.3 
6-3 
6.0 

5-8 
10.3 
16.1 
15-9 


20.9 
24.9 
20.1 
35-8 
16.8 
21. 1 
22.3 
17.13 
10.2 
8-5 


10.9 
10.9 

9-7 
7.6 


1.6 
I.I 

.2 

•S 
.6 

•3 
4.9 
9.8 
6.7 

2-3 

6.2 


•3 

•3 

14-3 

15.0 

25-1 

18.7 

1.0 

.8 

2-3 


-eg 


% 


1.6 
I.I 


2.0 
4.2 
3-7 

5-2 
1.2 

•4 


1.0 
2.4 
7.6 
^•7 


2.0 
2.0 

1-5 
.8 

1-7 

2-3 

1-7 


18.S 
14-3 
II-3 
9.9 

9-7 
2.0 
4.2 
1.9 
2.1 
I.I 


Calo- 
ries. 


995 
855 
985 

780 


470 
420 
225 

385 
300 

345 
570 
765 
650 

445 
710 


240 
215 
235 
225 

340 
425 
400 


430 

510 

1015 

1360 

1415 

915 

1250 

400 

290 

340 


24 


370 


SCIENCE    OF   NUTRITION. 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued), 


Kind  of  Food  Material. 


Edible  Portion. 


^5 
5^ 


Available  Nutrients. 


3   <^llO 


Animal  Foods. 

Eggs. 

Eggs,  uncooked 

Eggs,  boiled 


Vegetable  Foods. 
Cereals,  etc. 

Barley,  pearled 

Buckwheat  flour 

Buckwheat,  self-raising. . . 

Corn  (maize)  flour 

Corn  (maize)  meal 

Corn  (maize)  preparations 

Cerealine 

Hominy 

Hominy,  cooked 

Oatmeal  and  rolled  oats. . 

Oatmeal,  boiled 

Rice 

Rice,  boiled 

Rye  flour 

Entire  wheat  flour 

Gluten  flour 

Graham  flour 

Wheat  flour,  patent  proc- 
ess: 

Low  grade 

Baker's  grade 


% 

II. 2 
II. 2 


Dairy  products,  etc. 
Whole  m'ilk 

Skim  milk 

Condensed    milk,    sweet- 
ened  

Cream 

Cheese 

Butter 

Oleomargarine,  etc 

Lard,  cottolene,  etc 

Animal  Food. 

Miscellaneous. 

Gelatin 

•• 

Calf 's-foot  jelly 

% 

73-7 
73-2 

87.0 
90-5 

26.9 
74.0 
34-2 

II.O 

9-5 


13.6 
77.6 


"•5 
13.6 
II. 6 
12.6 
12.5 

10.3 
11.8 

79-3 
7.8 

84-5 
12.3 

72-5 
12.9 
11.4 
12.0 
II-3 


12.0 
11.9 


% 

I.I 
1.2 


•5 
•3 

1.2 
I.I 

3-4 
4.9 

5-7 
5-0 


3-2 
•3 


4.0 

3-5 
4.9 

3-6 
4.0 

4.2 
3-8 

•9 
5-6 

•9 
3-7 
I.I 

3-6 

4-5 
4.6 

4-7 


4-5 
4.2 


% 


13.0 
12.8 


3-2 
3-3 

8.5 
2.4 

25-1 


58.7 
4.2 


6.6 

5-2 
6.7 
58 
7-5 

7.8 

6.8 

1.8 

13-4 

2-3 

6-5 

2-3 

5-3 
10.7 
ii.o 
10.3 


10.9 
10.3 


% 
10. o 

II.4 

3-8 
•3 

7-9 
17.6 
32.0 
80.8 
78.9 
95-6 


i.o 
I.I 
I.I 
1.2 
1-7 

1.0 

•5 
.2 
6.6 
•S 
•3 


1-7 
1.6 


1-7 
1.4 


% 


5-0 
5-1 

54-1 
4-5 
2.4 


17.4 


76.1 
75-9 
71-5 
76.3 
73-5 

76.3 
76.9 
17.4 
65.2 

II-3 
76.9 
23.8 
76.9 
70.9 
70.1 
70.4 


70.2 
71.7 


% 


•5 
•5 

1.4 

•4 
2.9 

2-3 

4-7 


Calo- 
ries. 

695 

755 


310 
170 

1460 
860 
1885 
3410 
3335 
398s 


.6 

•5 

2125 
410 

.8 

•7 

1630 
1600 

.2 

•5 
.8 

1545 
1625 
1625 

•4 
.2 

•4 
•4 
•5 
•3 

1655 
1625 

375 
1795 

285 
1610 

■5 
.8 

7 
3 

505 
i6io- 

1645 
1630 
1640 

7 
5 

1635 
1640 

APPENDIX. 


371 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


Vegetable  Foods. 
Cereals,  etc. 

Family    and    straight 
grade 

High  grade 

Wheat  preparations: 

Breakfast  foods 

Macaroni 

Macaroni,  cooked  . 

Spaghetti 

Noodles 

Bread: 

Brown 

Com  (johnny cake). 

Rye..l 

Graham 

Whole  wheat 

White  wheat 

Biscuit,  soda* 

Rolls 

Toasted  bread 

Crackers: 

Boston  (split) 

Milk,  cream 

Graham 

Oyster 

Soda 

Water 

Cakes,  cookies,  etc.: 

Bakers'  cake 

Coffee  cake 

Gingerbread 

Sponge  cake 

Drop  cake 

Molasses  cookies. . 

Sugar  cookies 

Ginger  snaps 

Wafers 

Doughnuts 

Pie,  pudding,  etc.: 

Pie,  apple 

Pie,  custard 

Pie,  squash 


as 


% 


Edible  Portion. 


% 

12.8 
12.4 

9.6 
10.3 
78.4 
10.6 
10.7 

43-6 
38.9 
35-7 
35-7 
38-4 
35-3 
22.9 
29.2 
24.0 

7-5 
6.8 

5-4 
4.8 

5-9 
6.8 

31-4 

21-3 

18.8 

153 
16.6 
6.2 
8.3 
6.3 
6.6 
18.3 

42.5 
62.4 
64.2 


% 


4-5 
4-5 
1-3 
4.0 
4.2 

2.8 
3-5 
3-4 
3-4 
3-2 
3-3 
4-7 
3-6 
4.1 

5-0 
50 
4.8 

5-4 
4.9 

5° 

i-2, 
3-8 

4-3 
4.4 

4-5 
4-7 
4-5 
4-7 
4.8 
4.8 

31 
2.2 
2.4 


Available  Nutrients. 


% 


4.0       8.3 
4.0       8.7 


9-3 
10.4 

2-3 

9.4 
9.1 

4.2 
6.5 
7-3 
6.9 

7-5 
71 
7.2 
6.9 
8.9 

8.5 
7-5 
7-7 
8.8 
7.6 
8.3 

4.8 
5-5 
4-5 
4.8 

5-9 
5-6 
5-4 
50 
6.7 

5-2 

2-4 

3-2 

3-4 


% 


1.6 
.8 

1.4 
•4 
•9 

1.6 
4.2 

•5 
1.6 

.8 

1.2 

12.3 

3-7 

1-4 

7-7 
10.9 

8.5 
9-5 
8.2 

7-9 

4.1 
6.8 
8.1 
9.6 

13.2 
7.8 
9.2 
7-7 
7-7 

18.9 

8.8 

5-7 
7.6 


% 


73-5 
73-6 

74.0 

730 
15-6 
751 
74-3 

46.2 

45-2 
52.0 

51-3 
49.1 

523 
51.8 
55-8 
60.3 

69.9 
68.5 
72.5 
693 
71.8 
70.6 

55-8 
61.9 
62.1 

645 
59-2 
74.0 
71.6 
74-3 
730 
521 

41.8 
25.7 
21.4 


% 


•4 
•4 

i.o 
i.o 

1.0 

•5 
.8 

1.6 

1-7 
I.I 
I.I 
1.0 


1-3 

1.4 

1-3 
I.I 
2.2 
1.6 
1.4 

.6 

•7 
2.2 
1.4 

.6 

1-7 
1.0 
2.0 
1.2 
•7 

1.4 
.8 


=  0.110 


Calo- 
ries. 


1615 
1620 

1670 
1640 
405 
1640 
1640 

1035 
1 1 70 
1160 
1185 
1125 
"95 
1655 
1360 

1390 

1830 
1920 
1900 
1905 
1870 
1850 

1335 
1580 
1620 

1735 
1805 

185s 
1865 

1845 
1855 
1895 

1215 

795 
800 


•  Made  from  wheat  flour,  raised  with  baking  powder. 


'hl'2- 


SCIENCE    OE   NUTRITION. 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


Vegetable  Foods. 
Cereals,  etc. 
Pie,  pudding,  etc.: 

Pudding,  Indian  meal 
Pudding,  rice  custard. 
Pudding,  tapioca 


Sugars,  starches,  etc. 

Sugar,  granulated 

Sugar,  pulverized 

Sugar,  brown 

Sugar,  maple 

Molasses 

Maple  syrup 

Cornstarch 

Tapioca 

Sago 


Vegetables. 

Asparagus,  fresh 

Asparagus,  cooked 

Beans,  Lima,  green 

Beans,  Lima,  dried 

Beans,  string,  fresh 

Beans,  string,  cooked*... 

Beans,  white,  dried 

Beans,  baked 

Beets,  fresh -v 

Beets,  cooked* 

Beet  "greens,"  cooked*.. 

Cabbage 

Carrots,  fresh 

Carrots,  evaporated 

Cauliflower 

Celery 

Sweet  corn,  green 

Cucumbers 

Eggplant 

Lettuce 

Onions,  fresh 

Onions,  cooked* 

Parsnips 

Peas,  dried 


% 


Edible  Portion. 


55-0 


7.0 


15.0 
20.0 


20.0 
61.0 
15-0 

15.0 

lO.O 


Available  Nutrients. 


60.7 
59-4 
64-5 


94.0 
91.6 

68.5 
10.4 
89.2 

95-3 
12.6 
68.9 

87-5 
88.6 

89-5 
91-5 
88.2 

3-5 
92-3 
94-5 
75-4 
95-4 
92.9 

94-7 
87.6 
91.2 
83.0 
9-5 


% 


2-5 


•7 
i.o 
2.7 
6.7 
1.0 

•5 
7-5 
2.8 
1.0 
1.2 
1.2 

•7 
1.0 
6.9 

•7 

.6 

1.8 

■4 
.6 


7.6 


% 


4-5 

3-2 


•3 

7-7 


1-3 

1-7 

5-3 

12.8 

1-7 
.6 

15-8 
4.8 
1.2 
1-7 
1-7 
1.2 

•7 
5-8 
1-3 

.8 

2-3 

.6 

•9 

•9 

1.2 

•9 
1.2 

17-3 


% 


4-3 
4.1 
2.9 


3-0 

.6 

1.4 

•3 
1.0 
1.6 

2-3 

.1 

.1 

3-1 

■3 

•4 
3-2 

•5 
.1 

1.0 
.2 
•3 
•3 
•3 

1.6 

•5 
•9 


% 


26.9 

30-7 
28.2 


100. o 
100. o 

95-0 
82.8 
70.0 
71.0 
90.0 
88.0 
78.1 


3-3 
2.1 
21.6 
65.6 
7.2 
1.9 

59-9 

19.6 
9.4 
7.2 
3-2 
5-5 
8.9 

76.9 
4-7 
3-2 

19.0 

3-0 
4-9 
2.9 
9.6 
4.8 
13.0 
62.5 


% 


Calo- 
ries. 


785 
825 

715 


1790 
1790 
1700 
1485 
1255 
1270 

1715 
1685 
1665 


95 

19s 
525 

1565 

180 

90 

1530 
56s 
205 
170 
220 
140 
200 

1700 

13s 
80 

445 

75 

120 

85 

215 

175 

290 

1508 


*  With  butter,  etc.,  added. 


APPENDIX. 


0/0 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


Vegetable  Foods. 
Vegetables. 

Peas,  green 

Peas,  green,  cooked* 

Potatoes 

Potatoes,  cooked,  boiled.. 
Potatoes.       mashed      and 

creamed 

Pumpkins 

Radishes 

Rhubarb 

Squash 

Spinach,  fresh 

Spinach,  cooked* 

Sweet  potatoes,  fresh 

Sweet  potatoes,  cooked*.. 

Tomatoes 

Turnips 


Vegetables  {canjied). 

Asparagus 

Beans,  baked 

Beans,  string 

Beans,  Lima 

Sweet  corn 

Peas,  green 

Succotash 

Tomatoes 


/o 
45 -o 

20.0 


50.0 
30.0 
40.0 

50.0 


30.0 


25.0 
6.0 

35 -o 


Fruits,  etc.  (jresli). 

Apples 

Apricots 

Bananas 

Blackberries 

C"herries !    5.0 

Cranberries 

Currants 

Figs 

Grapes '  25.0 

Huckleberries j     . . 

Lemons .' 30.0 

Muskmelons 50.0 

Oranges 1  27.0 


Edible  Portion. 


74.6 
73-3 
7«-3 

75-5 

75-1 
93-1 
91.8 
94.4 

88.3 

92-3 
89.8 
69.0 
51-9 
94-3 
89.6 


94.4 
68.9 
93-7 
79-5 
76.1 

85-3 
75-9 
94.0 


84.6 
85.0 

75-3 
86.3 
80.9 
88.9 
85.0 
79.1 

77-4 
81.9 

«9.3 
«9.5 
86.9 

*  With  l)Ult 


2-5 

1.4 

1-7 

2.0 
.6 

•7 
.6 

•9 
1.0 
I.I 
2.1 
3-0 
•4 
.8 


.6 
2.7 

•7 
1-7 
1-7 
1.4 
1.8 

■5 


1.6 

1-5 
2.7 

1-5 
2.0 
1.2 

1-7 
2.2 
2.4 
2.0 
1.2 
I.I 
1.4 

cr,  i-lc. 


Available  Nutrients. 


5-2 
5-1 
1-7 
1.9 

2.0 

•7 
i.o 

•4 
I.I 
1.6 
1.6 

1-3 
2.2 

•7 
1.0 


1.2 

4.8 

.8 

3-0 
2.1 
2.7 
2.7 
•9 


•3 

•9 

1.0 

1.0 


•5 
.8 

•5 
.6 

(led. 


2-3 

.1 

•3 


>■  ,A 

-§S 

•^  2 

«-o 

'(A       1 

u 

< 

% 

% 

16.7 

.8 

14.4 

I.I 

17-7 

.8 

20.0 

.8 

17. 1 

I.I 

50 

•5 

5-6 

.8 

3-5 

•5 

8.6 

.6 

3-2 

1.6 

2.7 

I.I 

26.2 

.8 

40.3 

•7 

3-« 

•4 

7.8 

.6 

2.8 

•9 

19.7 

1.6 

3-7 

1.0 

14-3 

1.2 

18.3 

•7 

9.6 

.8 

18.0 

•7 

3-9 

•5 

12.8 

.2 

12.2 

•4 

19.9 

.6 

9.9 

•4 

I5-I 

•5 

8.9 

.2 

11.6 

•5 

17.0 

•5 

173 

•4 

14.9 

.2 

7-7 

•4 

8.4 

•5 

10.5 

•4 

Calo- 
rics. 

430 
490 

370 
415 

475 
no 

130 
100 
205 
100 
235 
545 
885 
100 
17s 

80 

555 
90 

335 
430 
235 
425 
100 


260 
240 
400 

235 
320 
190 
230 
330 
390 
300 
180 
160 


374 


SCIENCE   OF  NUTRITION. 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


Vegetable  Foods, 
Fruits,  etc.  (jresh). 

Pears 

Plums 

Prunes 

Raspberries,  black 

Strawberries 

Watermelons 


-a 


Edible  Portion. 


Fruits,  etc.  {dried). 

Apples 

Apricots 

Citron 

Currants 

Dates 

Figs 

Raisins 

Prunes 


Fruits,  etc.  {canned). 

Apricots 

Blackberries 

Blueberries 

Cherries 

Crab-apples 

Peaches 

Pears 

Strawberries  (stewed) 


Ntits. 

Almonds 

Butternuts 

Chestnuts  (fresh). 

Cocoanuts 

Filberts 

Hickorynuts 

Peanuts 


% 


5-0 
6.0 


6o.o 


lO.O 

15.0 


45 -o 
86.0 
16.0 
49.0 
52.0 
62.0 
25.0 


% 

84.4 
78.4 
79.6 
84.1 
90.4 
92.4 


28.1 
29.4 
19.0 
17.2 

15-4 
18.8 
14.6 
22.3 


81.4 
40.0 
85.6 
77.2 
42.4 
88.1 
81. 1 
74.8 


4.8 
4.4 

45 -o 
14.1 

3-7 
3-7 
9.2 


% 

1-7 
2.2 
2.1 

1-7 
1.0 

•9 


7-5 
7-7 
8-3 
8.6 
8.8 
8.7 
9.1 
8.3 


1.9 
6.1 
1.6 

2-3 

5-7 
1-3 
1.9 
2.6 


10.9 
11.4 

5-9 

9.2 

10.7 

10.6 

10.7 


Available  Nutrients. 


% 


•7 
1.4 


1-3 
3-7 
•4 
1.9 
1.6 

3-4 
2.0 
1.6 


17.8 

23-7 

5-3 

4.8 

I3-I 
21.9 


% 


2.0 

•9 

1-3 

1-5 

2-5 

•3 
3-0 


1.9 

■5 


49.4 

4.9 

45-5 
58.8 
60.7 
34-7 


% 

12.7 
18.2 
17. 1 
11.4 
6.8 
6.0 


59-6 
56.5 
70-3 
67.0 
70.7 
67.0 
68.7 
66.1 


15-7 
50-9 
"■5 
19. 1 
49.0 
9.8 
16.2 
21.7 


15.6 
3-2 
37-9 
25-1 
11.7 
10.3 
22.0 


% 

•3 
•4 
•5 

■5 
•5 


1.8 

■7 
3-8 
i.o 
1.8 
2.6 
1-7 


1-5 
2.2 
1.0 

1-3 
1.8 
1.6 

1-5 


Calo- 
ries. 

255 
345 
325 
270 
160 
125 


1 190 
1 130 
1340 
1315 
1415 
1290 
1410 
1230 


295 
1015 
240 
365 
985 
190 
310 
400 


2685 
2805 
990 
2460 
2930 
2980 
2255 


For  greater  detail  see  The  Chemical  Composition  of 
American  Food  Materials,  by  Atwater  and  Bryant,  Bulletin  28 
(Revised),  U.  S.  Dept.  of  Agriculture,  Washington,  1902. 


INDEX  OF  AUTHORS. 


Abderhalden  on  alcohol  in  medicine, 
227 

on  aniino-acids,  117 

on  composition  of  proteins,  358 

on  diet,  217 

on  effect  of  altitude  on  erythrocytes, 
266 

on  homogentisic  acid  output,  iig 

on  percentage  composition  of  pro- 
teins, 113 

on  protein  foods,  112 

on  purin  metabolism,  337 
Abderhalden  and  Bergell,  307 
Abderhalden  and  Bloch,  119 
Abderhalden  and  Rona,  114,  115,  116 
Abderhalden  and  Samuely,  116 
Abderhalden,  Bergell,  and  Doerping- 

haus,  74 
Abderhalden,  Gigon,  and  Strauss,  134 
Aders,  Levene,  and  Fischer,  113 
AUard,  274,  281 
Almagia,  341,  353 
Alsberg  and  Folin,  135 
Amberg  and  Morrill,  139 
Anderson,  269 

Anderson  and  Bergman,  268 
Anderson  and  Rosenau,  118 
Araki  on  lactic  acid  after  bloodletting, 
256,  258,  259 

on  phosphorus-poisoning,  308 
Armsby,  43 
Armsby  and  Fries,  49 
Asher  and  Rosenfeld,  274 
Atwatcr  on  calorimeter  for  man,  43 

on  diet,  211,  212,  221 

on  standard  values,  41 
Atwater  and  Benedict,  199,  225 
Atwater  and  Bryant  on  caloric  values, 

41 
on  composition  of  ordinary  food 

materials,  366-374 
Atwater  and  Rosa,  43 
Austrian  and  Jones,  339 


Babak,  95 
Bachl,  21 


Baer  and  Blum,  292,  294 
Baeyer,  277 
Bauer,  255 
Beebe,  30,  351 

Beger,  Fingerling,  and  Morgen,  237 
Benedict  on  alcohol  in  medicine,  227 
on  calorimetry,  43 
on  cutaneous  excretions,  22 
on  influence  of  glycogen  metabolism 

in  starvation,  56 
on  starvation,  56,  64,  65,  66,  67 
on  temperature,  85 
Benedict  and  Atwater,  199,  225 
Benedict  and  Carpenter,  200 
Benedict  and  Falta,  286 
Benedikt  and  Torok,  300 
Benjamin,  334 
Berg,  208 

Bergell  and  Abderhalden,  307 
Bergell,    Doerpinghaus    and    Abder- 
halden, 74 
Berger,  132 

Bergman  and  Anderson,  268 
Bernard  (C.)  on  diabetic  center,  271, 
272 
on    glycogen    after    protein    inges- 
tion, 142 
from  dextrose,  308 
from  protein,  128 
on  piqtire,  271,  272 
Bernstein,    Bolaffio,    and    Westenrijk 

on  D :  N  ratio  in  diabetes,  282 
Bidder  and  Schmidt  on  intermediary 
metabolism,  128,  129 
on  protein  metabolism,  20 
Billstrom,  Johansson,  and  Heyl,  176 
BischofT  and  Voit  (C.)  on  amount  of 
feces,  47 
on  carbon  elimination,  24 
on  gelatin,  iii 

on  heat  value  of  metabolism,  35 
on  nitrogen  in  urine,  23 
on  urea  excretion,  108 
Blauberg,  241 
Bleibtrcu  (Max),  176 
Bloch  and  Abderhalden,  119 
Blum,  X36 


375 


376 


INDEX    OF  AUTHORS. 


Blum  and  Baer,  292,  294 

Bolaffio,  Bernstein,  and  Westenrijkj  282 

Bornstein,  no,  117 

Bornstein  and  Miiller,  265 

Bowen  and  Higley,  202 

Boycott  and  Haldane,  264,  265 

Breuer  and  von  Seiller,  267 

Broden  and  Wolpert,  193 

Brown  and  Mendel,  350 

Brugsch,  69,  134 

Brugsch  and  Hirsch,  121 

Brunton  (L.),  340 

Bryant  and  Atwater  on  caloric  values, 

41  _ 

on  composition  of  food  materials, 
366-374 
Buchner  and  Meisenheimer,  309 
Bunge  on  ash  of  milk,  240 
on  composition  of  milk,  240 
on  growth  and  longevity,  252 
Burckhardt,  78 
Btirgi,  140,  207,  260 
Burian,  348,  349 

Burian  and  Schur  on  endogenous  uric 
acid  elimination,  344,  346 
on  integral  factor,  345 
on  purin  nitrogen  in  various  tis- 
sues, 348 
on  temperature  rise  due  to  purin 
bases,  2^;^ 


Camerer,  241,  249 

Camerer  (W.,  Jr.),  246 

Carpenter  and  Benedict,  200 

Cathcart,  69,  173 

Caspari,  Zuntz,  Loewy,    and   Mtiller, 
205 

Cecil,  283 

Chapin,  243 

Chittenden  on  diet,  218,  219,  220 
on  diet  and  uric  acid  output,  345 
on  nitrogen  equilibrium,  182 
on  protein  diet,  213,  214,  215 
on  work  and  protein  diet,  197 

Clapp  (Charles),  214 

Cohnheim,  147,  358 

Crawford,  32,  33 

Cramer    on    dextrose    increase    from 
glycerin  ingestion,  280 
on  diet,  238 
on  feces,  47 
on  pentoses,  303 
on  protein  foods,  143 

Cronheim,  116 

Cushny,  227 


Dakin,  294 

Daval  and  Patein,  242 

Dean  and  Henderson,  114 

Depretz,  33 

Dobson,  271 

Doerpinghaus,       Abderhalden,       and 

Bergell,  74 
Du  Bois-Reymond,  208 
Dulong,  33 

Durig  and  Zuntz  on  altitude  and  meta- 
bolism, 258,  261,  262,  263 
on  saturation  of  hemoglobin  with 
oxygen,  263 


Edkins  and  Langley,  77 

Ellinger,  137 

Embden,  275,  293 

Embden  and  Salomon,  278 

Embden,  Salomon,  and  Schmidt,  292 

Erben,  334 

Ewing,  305 


Falta  on  alcaptonuria,  136 
on  D  :  N  ratio  in  diabetes,  277 
on  dextrose  from  fat  in  diabetes,  282 
on  metabolism  in  diabetes,  283 
on  protein  food,  122 
on  treatment  of  diabetes,  302 

Falta  and  Benedict,  286 

Falta  and  Gigon,  121 

Falta  and  Neubauer,  137 

Falta,  Grote,  and  Staehelin,  160,  285 

Farkos,  228 

Feder,  120 

Fejes,  291 

Fick  and  Wislicenus,  195 

Fingerling,  Morgen,  and  Beger,  237 

Finkler,  255 

Fischer,  Levene,  and  Aders,  113 

Fischer  (B.),  305 

Fischer  (Emil)  on  composition  of  pro- 
tein, 59,  358 
on  composition  of  purin,  335 

Flack  and  Hill,  254 

Flourens  on  law  of  longevity,  251 

Fletcher  and  Hopkins,  254 

Folin    on    chemical    composition    of 
urines  on  purin-free    diets,    138, 
364     _ 
on  creatin  elimination,  140 
on  creatinin  excretion,  139 
on  diet,  217 

on  endogenous  protein  metabolism, 
139 


INDEX   OF  AUTHORS. 


377 


Folin  on  exogenous  protein   metabo- 
lism, 139 
on  influence  of  sugar  in  metabolism, 

on  protein  foods  and  nitrogen  ex- 
cretion, 13S 

on  reconstruction  of  ingested  pro- 
tein, 1 88 
Folin  and  Alsberg,  135 
Forster,  58 

Fraenkel  and  Geppert,  258 
Frank  and  Trommsdorf,  126,  132 
Frank  and  Voit  (F.),  90 
Frentzel,  79 

Frentzel  and  Reach,  203 
Freund  (E.),  66,  67,  68 
Freund  (O.),  66,  67,  68 
Friedenthal,  362 
Friedjung  and  Jolles,  241 
Friedmann,  136 
Fries  and  Armsby,  49 


Garrod,  351,  353 

Garrod  and  Hale,  137 

Geppert,  258 

Geppert  and  Fraenkel,  258 

Gibson,  84 

Gies  and  Hawk,  255 

Gigon  and  Falta,  121 

Gigon,  Abderbalden,  and  Strauss,  134 

Gogitidse,  238 

Goldbraith  and  Simpson,  84 

Graham,  214 

Grote,  Staehelin,  and  Falta,  160,  285 

Grube,  277 

G  ruber,  120 

Grund,  303 


Haas,  121 

Hagemann,  232 

Hagemann  and  Zimtz,  33 

Haldane  and  Boycott,  264,  265 

Hale  and  Garrod,  137 

Hamalainen  and  Helme,  122 

Hammarsten,  303 

Hanriot  and  Richet,  62 

Hansen  and  Hcnriques,  115 

Harrold  and  T^ee,  201 

Hartogh  and  Schumm,  280 

Hasselbalch,  229 

Hawk,  1 19 

Hawk  and  Gies,  255 

Hawk  and  Sherman,  141 


Heidenhain,  238 

HeijI,  Johansson,  and  Billstrom,  176 
Heilner,  118 
Heineman,  19S 
Hellsten,  201,  220 
Helme  and  Hamalainen,  122 
Helmholtz,  34 
Henderson  and  Dean,  114 
Henriques,  116 
Henriques  and  Hansen,  115 
Hermann,  48 
Herring  and  Simpson,  87 
Heubner,  245,  246 

Heubner  and  Rubner  on  metabolism 
of  children,  244,  246,  249 
on    percentage     composition     of 
cow  and  human  milk,  242 
Higley  and  Bowen,  202 
Hill  and  Flack,  254 
Hirsch  and  Brugsch,  121 
Hirsch,  Miiller  and  Roily,  314 
Hirschfeld,  216 
Hofmeister,  272,  358 
Hoogenhuyze  and  Verploeg,  139,  140, 

197 
Hopkins  and  Fletcher,  254 
Horbaczewski,  338 
Hiifner,  262 


Ibrahim  and  Soetbeer,  347 
Inagaki  and  Schwenkcnbecker,  320 


Jackson,  68 

Jackson  and  Mandel  (J.  A.),  137,  302 

Jackson  and  Pearce,  130 

Jacoby,  307,  308 

Jaffa,  216 

Jageroos,  232 

Janeway,  302 

Janeway  and  Oertel,  304 

Jensen,  172 

Johansson  on  carbon  dioxid  output, 
177 
on  chemical  regulation  of  tempera- 
ture, 100 
on  feces,  50 

on  metabolism  at  rest,  82 
on  night  and  day  metabolism,  81 
on  temperature  in  starvation,  84 
on  true  intestinal  work,  147 

Johansson  and  Koracn,  200,  202 

Johansson,  Billstrom,  and  Hcijl,  176 

Johansson,  Landergren,  Sonden,  and 
Tigerstedt,  50,  63,  66 


378 


INDEX   OF  AUTHORS, 


JoUes  and  Friedjung,  241 

Jones  (W.),  339 

Jones  and  Austrian,  339 

Jones  and  Partridge,  339 

Jordan,  237 

Joslin  on  acetone  in  diabetes,  291 


Katzenstein,  203,  205 

Kauffmann,  112 

Kermauner  and  Moeller,  5 1 

Kiesel,  240 

Kirschmann,  iii 

Kleiner  and  Underbill,  130 

Klemperer  on  albumosuria  in  fever, 

332 
on  gout,  352 
Klemperer  and  Umber,  305 
Klemperer  and  von  Leyden  on  meta- 
bolism in  pneumonia,  329,  330 
on  milk  diet,  325,  326,  327 
Knoop,  290 
Knopf,  278 

Kober  and  Levene,  121 
Kohler,  257 

Koraen  and  Johansson,  200,  202 
Korkunoff  and  Voit  (C.)  on  influence 
of  fat  on  nitrogen  retention,  168 
on  protein  and  carbohydrate  in- 
gestion, 178 
on  protein  food,  109 
Kossel  on  composition  of  protein,  358 
on  production  of  salmin,  60 
on  protein  end-products,  129 
Kossel  and  Steudel,  337 
Krehl  on  heat  rise  after  chill  in  fever, 
321 
on  metabolism  in  fever,  320 
on  water  evaporation  and  fever,  321 
Krehl  and  Matthes,  332 
Krummacher,  112,  195 
Kiilz,  79,  129,  172 
Kumagawa,  76 
Kumagawa  and  Miura,  55 
Kutscher,  358 


Landatj  on  alcohol  and  purin  meta- 
bolism, 351,  352 
on  fixed  integral  factor,  347 
Landergren  on  influence  of  cane  sugar 
on  metabolism,  173 
on   nitrogen   output    at   change   of 
diet  from  carbohydrate  to  fat,  184 
on  specific  nitrogen  hunger,  181 


Landergren  on  sparing    influence    of 

carbohydrates,  180 
Landergren,  Johansson,  Sonden,  and 

Tigerstedt,  50,  63,  66 
Lang,  320 

Langley  and  Edkins,  77 
Langstein  and  Meyer,  137 
Langworthy,  365 
La  Place,  18 

La  Place  and  Lavoisier,  32 
Laquer,  308 
Lavoisier  on  animal  heat,  32 

on  cold  and  metabolism,  9 1 

on  heat  and  respiration,  18,  19 

on  oxygen  and  metabolism,  253 
Lavoisier  and  La  Place,  32 
Lavonius,  206,  219 
Leathes,  291,  334 
Lee  and  Harrold,  201 
Lefevre,  loi,  318 
Lefmann,  140 
Lehmann,  50 
Lehmann  and  Zuntz,  62 
Lehmann  (C.)  and  Voit  (E.),  175 
Lemaire,  239 
Lesser,  114,  254 
Levene,  358 
Levene  and  Kober,  121 
Levene,  Fischer,  and  Aders,  113 
Lewinski,  77 
Lewinstein,  257 
Lhorisch,  53 
Lichtenfelt,  211,  216 
Liebermeister,  321 

Liebig  on  atmospheric  pressure  and 
metabolism,  253 

on  metabolism,  19 

on  nutrition,  18 

on  organic  chemistry,  20 

on  theory  of  metabolism,  359 
Lindemann  and  May,  304 
Linser,  355 

Linser  and  Schmid,  312,  313 
Litten,  330 
Lob  (W.),  309. 
Loewi  on  colloid-sugar,  273 

on  protein  metabolism,  113 

on  uric  acid  excretion,  347 
Loewy  on  excretion  of  amino-acids  at 
high  altitudes,  263 

on  work  and  protein   retention,  197 
Loewy  and  Zuntz,  262,  265 
Loewy,  Zuntz,  Miiller,  and  Caspar! 

205 
Lossen,  30 
Luciani  on  starvation,  55,  66,  77 


INDEX   OF    AUTHORS. 


379 


Luciani  on  temperature  in  starvation, 

82 
Ludwig,  19 

Lusk  on  alcohol  in  medicine,  227 
on  carbon  retention,  145 
on  creatinin  elimination,  139 
on  dextrose  from  glutamic  acid,  279 
on  influence  of  food  on  milk,  236 

of  work  on  metabolism,  201 
on  metabolism  in  diabetes,  286 
on  milk  secretion  in  starvation,  77 
on  origin  of  beta-oxybutyric  acid  in 

diabetes,  289 
on  phlorhizin  glycosuria,  281 
on  phosphorus-poisoning,  306 
on  tetanus  and  glycogen  output,  79 
on  withdrawal  of  carbohydrates,  179 
Lusk  and  Mandel  (A.  R.)  on  acetone 
excretion  in  diabetes,  296 
on  alphas  and  beta-colloid   dex- 
trose, 283,  284 
on  D  :  N  ratio  and  fat  burned,  280 
on  D  :  N  ratio  in  diabetes,  276 
on  dextrose  from  lactic  acid,  279 
on  fatal  ratio,  298 
on   lactic   acid   disappearance   in 

phlorhizin  glycosuria,  305 
on  levulose  in  diabetes,  301,  302 
on   nitrogen   elimination   in   dia- 
betes, 285 
on  severe  types  of  diabetes,  298 
on  yeast  in  diabetes,  301 
Lusk  and  Parker,  71,  133,  134 
Lusk  and  Ringer,  279 
Lusk  and  Stiles  on  colloid-sugar,  274 
on  D  :  N  ratio,  70,  276 
on  dextrose  from  pancreatic  di- 
gest of  meat,  278 
on  metabolism  in  diabetes,  273 
on  protein  food,  114 
on  sugar  in  diabetes,  129 
Lusk,  Ray,  and  McDermott,  307 
Lusk,    Reilly,   and    Nolan    on   avail- 
ability of  sugar  for  combus- 
tion, 130 
on  glycogen  in  starvation,  78 
on  metabolism  in  diabetes,  276 
on  protein  food,  iii 
Liithje  on  castration  and  metabolism, 
267 
on  D  :  N  ratio  in  diabetes,  277 
on  hvpothetica!  amino-sugars,  123, 

28i 
on  nitrogen  lag,  124,  186 
on  phosphoric  acid  retention,  186 
Luzzatto,  303 


MacCallum    on    parathyroidectomy, 

270 
Magnus  on  respiration,  19,  21 
Magnus-Levy   on   acetone   output   in 
diabetes,  296 
on  beta-oxybutyric  acid  and  acetone 
in  phlorhizin  diabetes,  295 
in  diabetes,  289,  291 
on  coma  in  diabetes,  297 
on  destruction  of  dextrose,  309 
on  gland  ingestion  in  gout,  354 
on  glycogen  in  liver  in  diabetes,  298 
on  gout,  351 

on  hippuric  acid  output,  134 
on  metabolism  in  diabetes,  295 
in  exophthalmic  goiter,  269,  283 
in  myxedema,  268 
on  oxygen  requirement  for  protein 
metabolism  in  diabetes,  288 
in  pregnancy,  230 
Mandel    (A.    R.)    on    metabolism    in 
fever,  333,  334 
on  starvation,  58 

on  uric  acid  elimination  in  aseptic 
fever,  332,  346 
Mandel  (A.  R.)  and  Lusk  on  acetone 
excretion  in  diabetes,  296 
on  alpha-  and  beta-colloid  dex- 
trose, 283,  284 
on  D  :  N  ratio  and  fat  burned, 
280 
in  diabetes,  276 
on  dextrose  from  lactic  acid,  279 
on  examination  of  severe  types  of 

diabetes,  298 
on  fatal  ratio,  298 
on   lactic   acid   disappearance   in 

phlorhizin  glycosuria,  305 
on  levulose  in  diabetes,  301,  302 
on   nitrogen   elimination   in   dia- 
betes, 285 
on  yeast  in  diabetes,  301 
Mandel  (J.  A.)  and  Jackson  on  glu- 
curonic acid,  302 
Mansfield  and  Woods  on  metabolism 
of  lumbermen,  200,  221 
on  protein  in  lumbermen's  ration, 
212 
Matthes  and  Krehl,  332 
May  on  metabolism  in  fever,  315,  323, 
328 
in  tuberculosis,  323 
May  and  Lindemann,  304 
Mayer,  280 
Mayer  (R.),  34 
Mayow,  18 


38o 


INDEX   OF   AUTHORS. 


McDermott,  Lusk,  and  Ray,  307 

Meeh,  88 

Meisenheimer  and  Buchner,  309 

Meissl  and  Strohmer,  174 

Mellanby,  139 

Meltzer,  130,  227 

Mendel  on  diet,  220 

on  digestibility  of  carbohydrates,  53 

on  protein  diet,  213 

on  uric  acid,  336 
Mendel  and  Brown,  350 
Mendel  and  Jackson,  137 
Mendel  and  Mitchell,  340 
Mendel  and  Rockwood,  117 
Mendel  and  Schneider,  137 
Mendel  and  White,  342 
Mendelson,  319 
Meyer  and  Langstein,  137 
Michaelis  and  Rona,  117 
Miescher  on  fat  ingestion,  166 

on  starvation,  58,  74 
Minkowski  on  diabetes,  272 

on   glycogen-free    livers   in   depan- 
creatized  dogs,  297 

on  gout,  352,  356 

on  levulose  in  diabetes,  301 

on  metabolism  in  diabetes,  275 

on  sugar  elimination  by  depancrea- 
tized  dogs,  275 

on  synthetic  uric  acid  in  liver,  348 

on  uric  acid,  338 
Minkowski  and  von  Mering,  272,  274 
Mitchell  and  Mendel,  340 
Miura  and  Kumagawa,  55 
Moeller  and  Kermauner,  5 1 
Mohr,  332 
Moleschott,  22 
Moore  and  Parker,  239 
Morgen,  237 

Morgen,  Beger  and  Fingerling,  237 
Moritz,  225,  272 
Morrill  and  Amberg,  139 
Mosso,  261 

Miiller  and  Bornstein,  265 
Miiller  (Friedrich)  on    beta-oxybuty- 
ric  acid,  292 

on  digestibility  of  bread,  5 1 

on  feces,  50 

on     metabolism     in     exophthalmic 
goiter,  268 

on  sugar  in  diabetes,  129 

on  toxic  action  upon  body  protein 
in  carcinoma,  323 
in  tuberculosis,  324 
in  typhoid,  324 
Miiller,  Hirsch,  and  Roily,  314 


Miiller,  Zuntz,  Loewy,  and  Caspar!, 

205 
Munk  on  diet,  212 

on   energy   requirement   in   starva- 
tion, 66,  67 
on  feces,  50 

on    nitrogen    and   phosphoric    acid 
secretion  in  starvation,  67,  68 
MurUn  on  creatin  elimination,  140 
on  glycocoll  retention,  123 
on  hypothetical  amino-sugars,  123, 

281 
on   metabolism   during   pregnancy, 

230,  232 
on  protein  condition,  185 
on  sparing  power  of  gelatin,   183, 
184,  1S5 


Naunyn,  330 
Nebelthau,  318,  319,  320 
Nencki  and  Schultzen,  188 
Nencki  and  Zaleski,  188 
Neubauer  on  alcap tonic  acids,  137 
on  levulose  in  diabetes,  301 
on  oxidation  of  amino-acids,  293 
Neubauer  and  Falta,  137 
Neuberg  on   butyric  acid  from   glu- 
tamic acid,  283 
on  metabolism  in  diabetes,  279 
on  pentoses,  303 
Neuberg  and  Salkowski,  303 
Nolan,   Reilly,   and    Lusk  on    avail- 
ability   of    sugar    for    com- 
bustion, 130 
on  glycogen  in  starvation,  78 
on  metabolism  in  diabetes,  276 
on  protein  food,  in 


Oertel  and  Janeway,  304 
Opie,  304 

Oppenheimer,  246,  247 
Oppenheimer  and  Reiss,  331 
Osborne,  112,  358 
Ostertag  and  Zuntz,  232,  248 
Oswald,  307 
Ott,  334 


Parker  and  Lusk,  71,  133,  134 
Parker  and  Moore,  239 
Partridge  and  Jones,  339 
Patein  and  Daval,  242 
Pearce  and  Jackson,  130 
Pembrey,  176 


INDEX  OF  AUTHORS. 


381 


Pettenkofer  on  respiration  apparatus, 

22,  23,  24 
Pettenkofer  and  Voit  (C.)  on  carbon 
and  urea  output,  36 
retention,  no 
on  fat  from  protein,  142 
on  heat  value  of  metabolism,  35 
on  influence  of  work  on  metab- 
olism, iqi,  194 
on  metabolism  in  diabetes,  286 
in  leukocythemia,  257 
in  starvation,  25,  26,  27,  28 
on  respiratory  quotient,  28 
on  starvation,  80 
PfeifTer,  341 
Pfeil,  349,  355 

Pfliiger  on  air  within  alveoli,  262 
on   dextrose  from  fat  in  diabetes, 

277,  278 
on  fat  ingestion,  166 
on  glycogen  in  starvation,  78 
on  metabolism  in  fever,  312 
on  oxygen  and  metabolism,  254 
on  protein  food,  107,  142 
on  respiration,  31 
on  sugar  elimination  by  depancrea- 

tized  dogs,  275 
on  theory  of  metabolism,  357 
Plimmer,  60 

Poda  and  Prausnitz,  108 
Pollack,  352 

Prausnitz  on  digestibility  of  carbohy- 
drates, 51 
of  foods,  53 
on  glycogen  in  starvation,  78 
on  starvation,  56 
Prausnitz  and  Poda,  108 


Ranke,  217 

Ray,  McDermott,  and  Lusk,  307 
Reach,  354 

Reach  and  Frentzel,  203 
Regnault  and  Reiset  on  oxygen  and 
metabolism,  28,  253 
on  respiration,  21,  23 
Reilly,  Nolan,  and  Lusk  on  availabil- 
ity of  sugar  for  combustion, 

on  glycogen  in  starvation,  78 
on  metabolism  in  diabetes,  276 
on  protein  food,  in 
Reiset  and  Rcgnauil  on  oxygen  and 
metabolism,  28,  253 
on  respiration,  21,  23 


Reiss  and  Oppenheimer,  331 

Rheinboldt,  268 

Richet  and  Hanriot,  62 

Rieder,  50 

Riehl  and  Weinland,  87 

Riethus,  321,  322 

Rietschel,  139 

Ringer,  265,  282 

Ringer  and  Lusk,  279 

Rockwood,  344,  349 

Rockwood  and  Mendel,  117 

Rohmann,  108 

Rohrig  and  Zuntz,  90 

Roily,  314 

Roily,  Miiller,  and  Hirsch,  314 

Rona  and  Abderhalden,  114,  115,  116 

Rona  and  Michaelis,  117 

Rosa  and  Atwater,  43 

Rosenau  and  AndersoUj  118 

Rosendahl,  265 

Rosenfeld  on  fat  from  protein,  305 

increase  in  starvation,  166 

metabolism,  296 

percentage  in  milk  in  starvation, 

77 

Rosenfeld  and  Asher,  274 

Rosenheim  on  diet,  212 

Rost  (E.),  249 

Rotch,  243 

Rubner  on  absolute  requirement,  148, 
149 
on  absorption,  241 
on  animal  calorimeter,  32,  42 
on  baths  and  douches,  10 1,  102 
on  caloric  value,  41,  42 

of  carbon,  144 
on  calories  of  average  dietaries,  161 
on  calorimetric  determinations,  36 
on  cane  sugar  and  metabolism,  173, 

on  carbon  dioxid  excretion,  146 

retention,  144 
on  cause  of  specific  dynamic  action, 

163 
on  chemical  regulation  of  tempera- 
ture, 92,  94,  100 
on  child's  metabolism,  243 
on  clothes  and  metabolism,  105 
on  cold  and  metabolism,  96 
on  compensation  theory,  148,  156 
on  constant  energy  expenditure,  250, 

251 
on  cow  and  human  milk,  242 
on  creatin  elimination,  140 
on  critical  tem[)erature,  93 
on  death  from  starvation,  74 


382 


INDEX   OF   AUTHORS. 


Rubner  on   diet,  211,  212,  213,  218, 

220,  222,  223,  224,  225 

on  digestibility  of  various  foods,  51 

on  dynamic  action  of  foodstuffs,  42 

on  effect  of  baths  on  metabolism,  312 

of  sun  rays  on  metabolism,  106 
on  energy  requirement,  210 
on  exclusive  meat  diet,  11 1 
on  external  temperature,  151,  152 
on  fat  ingestion,  166,  167,  168,  169 
on  feces,  46 
on  food  requirement  during  growth, 

228 
on  heat  value,  42 

and  body  surface,  39,  40 
of  carbohydrates,  41 
of  fat,  40 

of  feces,  37,  38,  52 
of  mixed  diet,  40 
of  protein,  37-39 
of  urine,  37 
on  humidity  and  heat  loss,  97,  98, 
99,  104 
and  metabolism,  96 
on  influence  of  work  on  metabol- 
ism, 192 
on  ingested  protein,  187 
on  ingestion  of  carbohydrates,  173, 

on  isodynamic  foodstuffs,  35 

replacement   of   fat   with    carbo- 
hydrates, 177 

on  law  of  skin  area,  89,  90,  359 

on  laws  governing  metabolism,  153 

on  maintenance  requirement,  162 

on  metabolism  in  diabetes,  287,  288 
in  phlorhizin  diabetes,  160 
of  fat  man,  103,  170 

on  milk  diet,  224 

on  minimum  requirement,  161 

on  nitrogen  equilibrium,  182 

on  outlets  for  heat,  91 

on  physical  regulation  of  tempera- 
ture, 93,  95 

on  protecting  layer  of  fat  and  tem- 
perature, 95 

on  protein  foods,  126,  142,  163 
requirement  of  cells,  186 

on  relation  of  weight  to  surface,  89 

on  secondary  rise,  151 

on  specific  dynamic  action,  149,  156, 
157,  158,  159,  361 

on  stages  of  metabolism,  150 

on  standard  fuel  values,  41 

on  sulphur  output,  141 

on  theory  of  metabolism,  359 


Rubner  on  water  elimination,  193,  320 
hunger,  55 
on  wear  and  tear  quota,  185 
on  wind  and  heat  loss,  102 
Rubner  and  Heubner  on  metabolism 
of  children,  244,  246,  249 
on  percentage  composition  of  cow 
and  human  milk,  242 


Salaskin  on  respiration,  21 
Salkowski  on  pentoses,  303 

on  uric  acid,  335,  342 
Salkowski  and  Neuberg,  303 
Salomon,  336 

Salomon  and  Embden,  278 
Salomon  and  Wallace,  50 
Salomon,  Schmidt,  and  Embden,  292 
Samuely  and  Abderhalden,  116 
Sanctorius,  17 
Sandelowsky,  331 
Sanford  (L.  C),  247 
Sawadowsky,  319 
Schafer,  238 
Schapiro,  249 
Scheele,  335 
Schittenhelm   on    purin    metabolism, 

339.  340,  341,  347 
Schittenhelm  and  Bendix,  343 
Schleich,  313 

Schliep  and  von  Noorden,  355 
Schlossmann,  243 
Schmid  and  Linser,  312,  313 
Schmidt  and  Bidder  on  intermediary 
metabolism,  128,  129 
on  protein  metabolism,  20 
Schmidt,  Salomon,  and  Embden,  292 
Schneider  and  Mendel,  137 
Schondorff,  72,  171,  172 
Schryver,  308 
Schultze,  358 
Schultze  (H.),  86 
Schultzen,  66 

Schultzen  and  Nencki,  188 
Schulz  on  death  drom  starvation,  75, 

on  fat  ingestion,  166 
Schumburg  on  carbohydrates   in  fa- 
tigue, 201 

on  coffee  and  tea  in  fatigue,  202 

on  work,  261 
Schumburg  and  Zuntz,  196,  206 
Schumm,  137 

Schumm  and  Hartogh,  280 
Schur  and  Burian  on  endogenous  uric 

acid  elimination,  344,  346 


INDEX   OF   AUTHORS. 


383 


Schur  and  Burian  on  integral  factor, 

345 
on  purin  nitrogen  in  various  tis- 
sue?, 348 
on  temperature  rise  due  to  purin 
bases,  333 
Schwenkenbecker  and  Inagaki,  320 
Seegen,  66 
Seeiig,  284 
Senator,  50 

Shaffer  on   carbohydrate   diet  in   ty- 
phoid, 328 
on  creatin  elimination,  140 
on  purin-free  diet,  iq6 
on  work  and  metabolism,  196,  197 
Sherman  and  Hawk,  141 
Simpson  and  Goldbraith,  84 
Simpson  and  Herring,  87 
Siven  on  diet,  212 

on  nitrogen  equilibrium,  178 
on  work  and  purin  metabolism,  350 
Siemens,  233 
Slowtzoff,  203 
Soetbeer,  354 

Soetbeer  and  Ibrahim,  347 
Soldner,  242 
Sonden,  50 

Sonden  and  Tigerstedt,  82 
Sonden,  Johansson,  Landergren  and 

Tigerstedt,  50,  63,  66 
Speck,  258 
Spitzer,  338 
Stadelman,  289 
Staehelin,  316 

Staehelin,  Falta,  and  Grote,  160,  285 
Staubli  on  alcohol  in  diabetes,  300 
on  beta-oxybutyric  acid  output  in 

diabetes,  296,  297 
on  levulose  in  diabetes,  302 
Steudel,  348 
Steudel  and  Kossel,  337 
Steyrer,  269 

Stiles  and  Lusk  on  colloid-sugar,  274 
on  D  :  N  ratio,  70 

in  diabetes,  276 
on  dextrose  from  pancreatic  di- 
gest of  meat,  278 
on  metabolism  in  diabetes,  273 
on  protein  food,  114 
on  sugar  in  diabetes,  129 
Stockvis,  240 
Stohmann,  36,  40 

Straub  on  carbon  monoxid  diabetes, 
284 
on  water  and  protein  metabolism, 
118 


Straub  on  water  hunger,  54 
Strauss,  Abderhalden,  and  Gigon,  134 
Strohmer  and  Meissl,  174 
Siindstrom,  221 
Sydenham,  351 


Tallquist,  179,  180 

Tangl  on  absorption  of  energy  con- 
stituents of  milk,  241 
on  food  requirement  during  growth, 
228,  229 

Thiele,  135 

Tigerstedt  on  feces,  50 

on  metabolism  and  work  in  starva- 
tion, 81,  82 

Tigerstedt  and  Sonden,  82 

Tigerstedt,    Johansson,    Landergren, 
and  Sonden,  50,  63,  66 

Torok  and  Benedikt,  300 

Traube,  318 

Trommsdorf  and  Frank,  126,  132 

Tuczec,  66 


Umber  and  Klemperer,  305 
Underbill  and  Kleiner,  130 


Van  Slyke,  242 

Verploeg  and  Hoogenhuyze,  139,  140, 

197 
Viault,  266 
Virchow,  305 
Vogt,  354 

Voit  (C.)  on  amount  of  feces,  47 
on  calorimeter,  36 
on  cause  of  metabolism,  30 
on  chemical  regulation  of  tempera- 
ture, 92,  99 
on   circulating  and  organized  pro- 
tein, 58 
on  definition  of  food,  107,  211 
on  diet,  211,  212,  216,  218,  219,  220, 
221,  238 
and  milk  secretion,  235 
on  fat  from  protein,  305 

ingestion,  165,  168 
on  gelatin,  60 
on  glycogen,  171 
on  heat  value  of  metabolism,  35 
on  increased  ingestion  of  meat,  no 
on  influence  of  work  on  metabolism, 

193 
on  ingestion  of  carbohydrates,  171, 

172,  174 


384 


INDEX  OF  AUTHORS. 


Voit  (C.)  on  meat  extract,  140 

ingestion,  108 
on  metabolism,  23,  29,  43 

in  diabetes,  286 
on  nature  of  feces,  46 
on  nitrogen  at  lactation,  234 

equilibrium,  20 

output  by  hair  and  skin,  22 
on  organs  attacked  in  starvation,  76 
on  protein  foods,  116,  120,  128,  129 

metabolism  in  starvation,  80 

requirement,  167 
on  quantity  of  combustion,  359 
on  respiration,  21 
on  rise  in  carbon  dioxid  excretion, 

146 
on  temperature  and  metabolism,  too 
on  theory  of  metabolism,  357 
on  urea  elimination  in   starvation, 

57 
Voit  (C.)  and  Bischoff  on  amount  of 
feces,  47 
on  carbon  elimination,  24 
on  gelatin,  in 

on  heat  value  of  metabolism,  35 
on  nitrogen  in  urine,  23 
on  urea  excretion,  108 
Voit  (C.)  and  Pettenkofer  on  carbon 
and  urea  output,  36 
retention,  no 
on  fat  from  protein,  142 
on  heat  value  of  metabolism,  35 
on  influence  of  work  on  metabol- 
ism, 191,  194 
on  metabolism  in  leukocythemia, 
257 
in  starvation,  25,  26,  27,  28 
on  respiration  in  diabetes,  286 
on  respiratory  quotient,  28 
on  starvation,  80 
Voit  (E.)  on  death  from  starvation, 
72,  74,  75 
on   energy   requirement   in   starva- 
tion, 65 
on  glycogen  after  starch  diet,  143 
on  heat  value  and  body  surface,  40 
on  ingestion  of  carbohydrates,  175 
on  law  of  skin  area,  89 
on  nitrogen  elimination  in  starva- 
tion, 61 
on  organs  attacked  in  starvation,  76 
on  protein  metabolism,  73 
on  regulation  of  tem7)erature,  95 
on  temperature  regulation,  86,  87 
Voit  (E.)  and  Korkunoff  on  influence 
of  fat  on  nitrogen  retention,  168 


Voit  (E.)  and  Korkunoff  on  protein 
and     carbohydrate     ingestion, 
178 
on  protein  food,  109 
Voit  (E.)  and  Lehmann  (C),  175 
Voit  (F.)  on  metabolism  in  fever,  313, 

314 
in  myxedema,  268 
on  source  of  feces,  48,  49 
Voit  (F.)  and  Frank,  90 
Von  Bergmann,  267 
Von  Hosslin,  325 

Von   Jaksch,   on  phosphorus  poison- 
ing, 309  _ 
on  purin  bodies  in  tuberculosis,  333 
on  rhamnose  in  diabetes,  304 
Von  Leyden,  331 

Von  Leyden  and  Klemperer  on  meta- 
bolism   in    pneumonia,   329, 

330 
in  typhoid,  327 
Von  Mering,  273 

Von  Mering  and  Minkowski,  272,  274 
Von  Mering  and  Zuntz,  146 
Von  Noorden  on  acetone  and  beta- 
oxybutyric  output  in  diabetes, 
297 
output  in  diabetes,  296 
on  intensity  of  diabetes,  298 
on  levulose  in  diabetes,  301 
on  metabolism  in  diabetes,  282 
on  opium  in  diabetes,  301 
on  pancreas  in  diabetes,  304 
Von  Noorden  and  Schliep,  355 
Von  Schrotter  and  Zuntz,  260 
Von  Seiller  and  Breuer,  267 
Von  Terray,  259 
Von  Winckel,  230 


Wakeman,  307 

Waldvogel,  307 

Wallace  and  Salomon,  50 

Ward,  264 

Weinland,  145,  176 

Weinland  and  Riehl,  87 

Welch,  330 

Wells,  118 

Westenrijk,   Bernstein,   and   Bolaffio, 

282 
White,  243 

White  and  Mendel,  342 
Wiechowski,  343,  347 
Wiener,  341 
Willis,  271 
Wilson  (M.  B.),  247,  248,  250,  251 


INDEX  OF   AUTHORS. 


385 


Wislicenus  and  Fick,  195 

Wohler,  357 

Wolf  (C.  G.  L.),  124,  135,  142 

Wolffberg,  128 

Wolgemuth,  307 

WoUaston,  335 

Wolpert,  102 

Wolpert  and  Broden,  193 

Wood,  317 

Woods  and  Mansfield  on  metabolism 

of  lumbermen,  200,  221 
on  protein  in  lumbermen's  ration, 

212 
Workman,  261 


Zacharjewski,  233 
Zaleski  and  Nencki,  188 
Ziegler,  331 
Zitowitsch,  226 
Zuntz  on  anemia,  255 

on  apparatus  for  determining  car- 
bon dioxid  output,  62 
on  effect  of  altitude  on  hemoglobin, 
266 
of  sunlight  on  metabolism,  106 


Zuntz  on  effect  of  training  on  meta- 
bolism, 208 
of  work  on  metabolism,  198 
on  feces,  50 

on  metabolism  and  speed,  205 
on  oxygen  and  metabolism,  254 
on    renal    character    of    phlorhizin 

glycosuria,  273 
on  starvation,  79 

on  thickness  of  alveolar  and  capil- 
lary walls,  253 
Zuntz  (L.),  208,  259,  260,  261 
Zuntz  and  Durig  on  altitude  and  meta- 
bolism, 258,  261,  262,  263 
on  saturation  of  hemoglobin  with 
oxygen,  263 
Zuntz  and  Hageman,  33 
Zuntz  and  Lehmann,  62 
Zuntz  and  Loewy,  262,  265 
Zuntz  and  Ostertag,  232,  248 
Zuntz  and  Rohrig,  90 
Zuntz  and  Schumburg,  196,  206 
Zuntz  and  von  Mering,  146 
Zuntz  and  von  Schrotter,  260 
Zuntz,  Loewy,  Miiller,  and  Caspari, 
20s 


as 


NDEX  OF  SUBJECTS. 


Abundant  diet,  148 

nutrition  stage  of  protein  metabol- 
ism, 150 
Aceto-acetic  acid  in  diabetes,  origin, 

289 
Acetonuria  in  diabetes,  289 

in  starvation,  69,  70 
Adenase,  339 
Adenin,  335,  336 
Affinities,  cell,  360 
Air,  heat  loss  by  warming,  91 
Albuminuria  in  starvation,  70 
Alcaptonic  acids,  136,  137 
Alcohol  as  substitute  for  carbohydrates 
and  fat,  225 

gout  and,  351 

in  diabetes,  300 

influence  of,  on  metabolism,  225 

stimulating  power  of,  202 
Alimentary  glycosuria,  272 
Alkaptonuria,  136 

fixed  diet  and  water  in,  119 
AUantoin,  338 

and  uric  acid,  relation,  342 
Altitudes,  high.      See  High  altitudes. 
Alveoli,    ox}'gen    and    carbon    dioxid 

pressure  within,  262 
Ainino-acids,    breaking    up    proteins 
into,  113,  186 

conversion  into  dextrose,  278 

deaminization  of,  129,  163 

ingestion  of,  113 

oxidation  of,  293 

regeneration  of,  into  protein,  60, 188 

specific  dynamic  action  of,  160 

tryptophan  in  nitrogen  equilibrium, 
116 
Amino-sugars,  123,  124 
Ammonia  output  in  starvation,  68,  69 

absence  of,  in  breath,  21 
Anabolism,  19 
Anaphylaxis,  117 
Anemia,  metabolism  in,  253 
Animal  calorimeter,  42 

foods,  digestiVjility  of,  53 

heat,  32 

proteins,  composition,  112 


Animals  of  similar  shapes,  determin- 
ing surface  of,  88 

Appetite  in  fever,  324 

protein  ingestion  and,  218 

Armsby's  calorimeter  for  cattle,  43 

Artificial  foods,  108 

Ascaris,  fatty  acid  from  glycogen  by 
action  of,  176,  255 

Aseptic  fever,  311 

Assimilable  protein  nitrogen,  45,  211 

Atmosphere,  composition,  258 
pressure  of,  258 

Atmospheric    pressure,    blood    circu- 
lation and,  265 
mechanical  work  and,  260,  261 
reduced,  cyanosis  from,  264 

Auto-intoxication,  death  from  starva- 
tion and,  76 

Autolysis,  307 

Avoirdupois  and  metric  weights,  com- 
parison, 364 


Basal  requirement  for  energy,  98 
Baths,  cold,  metabolism  and,  lor,  318 

reaction  from,  318 
Bed  ridden,  diet  for,  222 
Beer,  German,  226 
Beta-oxybutyric  acid,  coma  and,  289 
elimination  of,  297 
origin,  in  diabetes,  289 
output  in  starvation,  69 
Bile  flow  in  starvation,  77 

taurin  of,  cystin  and,  136 
Blood   circulation,   atmospheric  pres- 
sure and,  265 
hemoglobin  of,  saturation  with  air, 

262,  263 
plasma  in  starvation,  77,  78 
supply  to  skin,  temperature  and,  88 
Bloodletting,  metabolism  and,  255 
Blood-serum,  influence  of  ingestion  of 
gliadin  on  proteins  of,  116,  117 
injection    into   blood-vessels,   nitro- 
gen elimination  in,  58,  117 
Body  area,  heat  value  of  metabolism 
and,  39 


387 


388 


INDEX   OF   SUBJECTS. 


Bone  diet,  effect  on  color  of  dog  feces, 

46 
Brain  restorers,  141 
Bread,  effect  on  feces,  48 

white,  as  exclusive  diet,  225 
Butter,  heat  value,  40 


Calcium  hunger,  54 
of  milk,  241 
output  in  starvation,  67 
Caloric  value,  41 

metabolism  and,  44,  45 

of  butter,  40 

of  cane  sugar,  41 

of  carbohydrates,  41 

of  dextrose,  41 

of  diet,  calculation,  223,  224 

of  feces,  37,  52 

of  foodstuffs,  35,  36 

of  meat,  126,  127 

of   metabolism,    surface    area    of 

body  and,  39 
of  milk,  241,  242,  243 

sugar,  41 
of  mixed  diet,  40,  41 
of  neutral  fats,  40 
of  olive  oil,  40 
of  protein,  36,  39,  40 

source  of,  129 
of  retained  carbon,  144,  146 
of  starch,  41 
of  sugar,  41 
of  urine,  37 
Calories,  percentages  in  different  diets, 

161 
Calorific  equilibrium,  161 
Calorimeter,  animal,  42 
cattle,  43 
human,  36,  43 
Calorimetry,  direct  and  indirect,  com- 
parison, 42,  64 
Cane  sugar,  heat  value,  41 
metabolism  and,  173 
specific  dynamic  action  of,  160 
Carbohydrate,    carbon,    retention    of, 

diet,  high,  in  fever,  327-329 

in  diabetes,  296 
metabolism,  309 

d-glucuronic  acid  and,  302 

pentoses  and,  302 
requirement  in  hepatic  disease,  180, 

309 
Carbohydrates,  affinities  for,  360 
amount  in  diet,  219 


Carbohydrates    and    fat,    alcohol    as 
substitute,  225 
interchangeability  in  nutrition,  35 
relative  value  for  mechanical  en- 
ergy, 198 
as  isodynamic  equivalent  of  fat,  177 
as  source  of  carbon  dioxid,  26 

of  energy,  178 
conversion  into  fat,  174 
digestibility  of,  51 
glycocoU   ingested   with,   retention, 

123 
heat  value,  41 
ingestion  of,  influence,  171 
in  liver  diseases,  180,  309 
mechanical  work  and,  201 
nitrogen  equilibrium  and,  178 

retention  and,  186 
partial  replacement  with  fat,  179 
sudden  withdrawal,  protein  metab- 
olism and, 179 
tolerance  of,  in  diabetes,  299,  300 
Carbon,  carbohydrate,  retention,  174 
dioxid,  amount  excreted,  19 

and   oxygen   pressure   within   al- 
veoli, 262 
carbohydrates  as  source  of,  26 
expired  and  oxygen  inspired,  re- 
lation, 23,  28,  30 
fats  as  source  of,  26 
from  ingested  meat,  elimination 

in  respiration,  126 
output,  determining,  62 
during  work,  192 
evenness  of,  132 
in  fever,  314 
in  starvation,  62 

compared  with  temperature 

changes,  82-85 
day  and  night,  81,  82 
mechanical  work  and,  200,  202 
of  infant,  244 

sugar  ingestion  and,  176,  177 
production  from  work,  elimina- 
tion, 202 
equilibrium  in  increased  meat  diet, 
no 
nitrogen  equilibrium  and,  109 
monoxid  diabetes,  284 
retained,  144,  145 
caloric  value  of,  144 
Casein    injections,    metabolism    and, 

"7 
specific  dynamic  action  of,  160 
Castration,  metabolism  and,  267 
Catabolism,  19 


INDEX   OF  SUBJECTS. 


389. 


Cattle  calorimeter,  43 
Cell  affinities,  360 
Cereals,  digestibility  of,  51 
Chemical    comparison    of    urines    on 
purin-free  diets,  364 
regulation  of  temperature,  88,  92, 

99 
during  work,  92,  193 

Child,  metabolism  of,  weight  and,  243 

Childbirth,  protein  metabolism  before 
and  after,  234 

Chill,  fever  rise  after,  321 

Chlorin  output  in  starvation,  67,  68 
in  fever,  331 

Circulating  protein,  58,  60 

Cleavage  products,  proteolytic,  60,  113 

Climate,    racial    characteristics    and, 
104 

Clonic     convulsions     after    parathy- 
roidectomy, 270 

Clothes  in  temperature  regulation,  104 
metabolism  and,  105 

Coffee,  recuperative  power  of,  202 

Cold  baths,  metabolism  and,  loi,  318 
reaction  from,  318 
external,     temperature     regulation 

and,  88 
metabolism  increase  and,  91 
sugar  output  in  diabetes  and,  281 

Coma,  beta-oxybutyric  acid  and,  289 
in  diabetes,  289 

Compensation  theon.',  148,  156 

Conduction  as  path  of  heat  loss,  91 

Conservation  of  energy,  law  of,  34 

Corpora  striata,  heat  puncture  of,  314 

Cost    of    protein    and    energy,    table 
showing,  365 

Cow  and  human  milk,  relative  com- 
position, 241,  242 

Cow's  milk,  dilution  of,  243 

Cream   with   mixed  diet  for  nursing 
mothers,  239 

Creatin    as    index    of    breakdown    of 
muscle,  140 
conversion    in    Liebig's   extract   of 

beef,  140 
elimination,  138 

in  starvation,  69 
in  urine,  138 

Creatinin  elimination,  138 
in  starvation,  69 
in  urine,  138 

Crystalline   vegetah)lc    proteins,    com- 
position of,  112 

Cyanosis    from    reduced  atmospheric 
pressure,  264 


Cystin,  bile  taurin  and,  136 

elimination,  protein  food  and,  135 
in  urine,  135 

Cystinuria,  artificial,  135 


Day    and    night    metabolism,    work 

and,  81 
Deamination,  seat  of,  135,  188 
Deaminized     remainder    of     protein, 

20,  129,  163 
Decomposition  within  body,  19 
Denitrogcnized  remainder  of  protein, 

20, 129,  163 
Depancreatization,  diabetes  from,  272, 

274 
Development,  energy  for,  228 
Dextrose  and  nitrogen  excretion,  meat 
ingestion  in  diabetes  and,  130 
ratio  in  diabetes,  131,  275,  283 

fat  from,  310 

from  amino-acids,  278 

from  lactic  acid,  279 

glycogen  from,  171 

heat  value,  41 

in  starvation,  77 

lactic  acid  from,  308,  309 

production  and  nitrogen  output  in 
starvation,  ratio,  70 
i-glucuronic  acid,  carbohydrate  meta- 
bolism and, 302 
Diabetes,  aceto-acetic  acid  in,  origin, 
289 

acetonuria  in,  289 

alcohol  in,  300 

beta-oxybutyric  acid  in,  origin,  289 
elimination  in,  297 

carbohydrate  diet  in,  296 
tolerance  in,  209,  300 

carbon  dioxid,  284 

causes,  272 

coma  in,  289 

diet  in,  300 

drugs  in,  300,  301 

emaciation  in,  284 

energy  requirement  in,  300 

ether,  284 

extirpation  of  pancreas  and,  272,  274 

fat,  combustion  in,  296 
requirement  in,  300 

fatal  ratio  in,  299 

glycogen  from  protein  and,  129 

glycosuria  and,  distinction  between, 

273 
influence    on    protein    metabolism, 
284,  285 


390 


INDEX  OF   SUBJECTS. 


Diabetes,  intensity  of,  determination, 

298 
islands  of  Langerhans  and,  304 
levulose  in  treatment  of,  301,  302 
levulosuria  in,  301 
meat  ingestion  in,  dextrose  and  ni- 
trogen elimination  in,  130 
mechanical  work  in,  201 
mellitus,  272 
metabolism  in,  271 

perverted,  295 
nitrogen  and  dextrose  ratio  in,  131, 

2  75>  .283 
opium  in,  300,  301 
pancreas,  experimental,  272,  274 
pentoses  and,  302 

protein  in,  specific  dynamic  action 
of,  281,  287,  288 

metabolism  in,  160,  185,  186 
respiratory  quotient  of  protein  in, 

288 
severe  types,   clinical  examination, 

299  _ 
starvation,  272 
sugar  in,  exposure  to  cold  and,  281 

fat  metabolism  and,  277,  280 
test-diet  in,  298 
thyroids  and,  283 
treatment,  300 
Diabetic  center,  272 

puncture  of,  271 
Diarrhea  from  albumoses,  116 
from  peptoses,  116 
from  proteolytic  cleavage  products, 

116 
Diet,  abundant,  148 
at  high  altitudes,  264 
caloric  value,  calculation,  2123,  224 
calories  percentages  in,  161 
carbohydrate  in,  219 

high,  in  fever,  327-329 

in  diabetes,  296 
fat  in,  219 
feces  and,  50,  52 
for  bed  ridden,  222 
for  farmers,  221 
for  fat  people,  1 10 
for  hard  workers,  221 
for  light  work,  220 
for  nursing  mothers,  239 
for  ordinary  laborers,  220 
for  soldier  at  drill,  219,  220 
for  summer,  217 
high  and  low  protein,  nitrogenous 

urinary  constituents  and,  138 
in  diabetes,  300 


Diet  in  fever,  324 
in  gout,  356 
in  pregnancy,  230 

influence  on  composition  of  milk, 
235>  236 
explanation,  238 
maintenance,  148 
milk,  224 

fat  and,  236,  238 
in  fever,  325 
in  obesity,  225 
sugar  and,  236 
mixed,  gelatin  substituted  for  pro- 
tein in,  effect  of,  183 
heat  value,  40,  41 
sulphur    and    nitrogen    elimina- 
tion, 141 
non-protein,  in  fevers,  163 
■    normal,  210 
of  eggs,  224 
of  white  bread,  225 
previous,   influence  on   urea  elimi- 
nation in  starvation,  57 
proper  proportion,  211 
protein,  high,  in  fever,  326 

in  summer,  restriction  of,  163 
purin-free,  344 

chemical    comparison    of    urines 
on,  364     _  _ 

to  determine  intensity  of  diabetes, 
298 
Dietaries,  hospital,  223 

standard,  222 
Digestibility  of  carbohydrates,  51 
Douches,  metabolism  and,  loi 
Drinking,  water,  protein  metabolism 

and, 118 
Dynamic  action  of  foodstuffs,  specific, 
156.     See  also  Specific  dynamic 
action. 
of  metabolism,  42 
of  protein,  secondary,  151 
protein  metabolism,  186 
quota,  185,  187,  188 
Dyspnea  from  decrease  of  oxygen,  257 


Edestin,    intravenous    injection    of, 

metabolism  and,  117 
Egg  diet,  224 

energy  in,  228 

respiratory  quotient  of,  229 
Emaciation  in  diabetes,  284 
Endogenous  protein  metabolism,  139 

purin  bases,  344 
source,  348 


INDEX  OF  SUBJECTS. 


391 


Endogenous  uric  acid,  344 

Energ\%  34 

basal  requirement  for,  98 
conservation  of,  law  of,  34 
equivalents,  comparative,  203,  204 
expenditure,  constant  law  of,  250 
for  development,  228 
from  protein,   table   showing    cost, 

365 
ingested,  retention  of,  249,  250 

kinds  of,  34 

mechanical,  34 

of  pregnancy,  229,  230 

ontogenetic,  228 

potential,  34 

requirement,  148,  210,  361 
in  diabetes,  300 

source  of,  194,  195,  196 
on  earth,  34 

sun's,  34 

values,  36.     See  also  Caloric  value. 
Erysipelas,  metabolism  in,  315 
Ether  diabetes,  284 
Evaporation  of  water,  heat  loss  by,  91 
Exercise  at  high  altitudes,  263 

muscular  hypertrophy  from,  197 

oxygen  absorption  during,  190 

purin  metabolism  and,  349 
Exogenous  protein  metabolism,  139 

purin  bases,  344 

uric  acid,  344 
Exophthalmic    goiter,    glycosuria    in, 
283 
metabolism  in,  268 
External  cold,  temperature  regulation 

and,  88 


Farmers,  diet  for,  221 

Fasting,  55.     See  also  Starvation. 

Fat,  affinities  for,  360 

alone  in  starvation,  180,  181 
amount  in  diet,  219 
and  carbohydrates,  alcohol  as  sub- 
stitute, 225 
and  carbohydrates,  interchangeabil- 
ity  in  nutrition,  35 
relative     value     for     mechanical 
energy,  198 
and  meat  ingestion,  167,  168 

absence  of  secondary  rise  in  fat 

metabolism,  169 
secondary  rise  in    protein  me- 
tabolism, 169 
and  protein  metabolism  in  starva- 
tion, 72,  73 


Fat  as  source  of  carbohydrates,  174 
of  carbon  dioxid,  26 
carbohydrates  as  isodynamic  equiv- 
alent of,  177 
combustion  in  diabetes,  296 
content  of  milk,  diet  and,  236 
explanation,  239 
fasting  and,  236 
conversion  into  sugar  for  mechani- 
cal work,  198,  199,281 
of  carbohydrates  into,  174 
effect  on  feces,  48 
from  dextrose,  310 
in  milk,  substitution  of  milk  sugar 

for,  248 
ingested,  appearance  in  milk,  238 
ingestion,  influence  of,  165 
nitrogen  retention  and,  168 
object  of,  189 
man,  diet  for,  no 

effect  of  temperature  and  humid- 
ity on  metabolism  of,  103 
moisture  evaporation  in,  103,  193 
metabolism,   absence  of  secondary 
dynamic  rise   in,  on    meat-fat 
diet,  169 
sugar  in  diabetes  and,  277,  280 
milk,  production  by  infiltration,  239 

from  protein,  235 
neutral,  heat  value,  40 
partial     replacement    of     carbohy- 
drates by, 179 
production      from     carbohydrates, 

174 
from  protem,  142,  304,  305 
requirement  in  diabetes,  300 
specific  dynamic  action  of,  158,  165 
subcutaneous,  temperature    regula- 
tion and,  93,  95 
Fatal  ratio  in  diabetes,  299 
Fatigue,  oxygen  inhalations  in,  254 
Fatty  acid,  oxidation  of,  290 
degeneration,  305 

in  fever,  330 
infiltration  from  lessened  sugar  com- 
bustion, 257,  304 
Fecal  nitrogen,  48,  49 
Feces,  amount,  47 
diet  and,  48,  49 
caloric  value  of,  37 
collection  of,  46 
constitution  of,  early  study,  20 
diet  and,  50 
dog,  bone  diet  and,  46 
effect  of  bread  diet,  48 
of  fat  in  diet,  48 


392 


INDEX   OF   SUBJECTS. 


Feces,  effect  of  lampblack  on  color  of, 

of  sugar  in  diet,  48 
from  different  diets,  52 
from  meat  and  rice  diet,  51,  52 
from  rice  diet,  51 
heat  value  of,  52 
human,  50 
in  starvation,  47 
milk  diet  and,  46 
nature  of,  45 
normal,  51,  52 
production  in  man,  50 
silicic  acid  diet  and,  47 
source,  48 

starch  particles  in,  5 1 
Fever,  amount  of  metabolism  and,  321 
appetite  in,  324 
aseptic,  311 

carbohydrate  diet  in,  high,  327-329 
carbon  dioxid  output  in,  314 
causes,  312 
combating,  318 
definition,  311 
diet  in,  324 
etiology,  332 

fatty  degeneration  in,  330 
forced  feeding  in,  325 
heat  loss  and,  316,  318 
in  tuberculosis,  323 
induced,  metabolism  in,  315,  317 

by  erysipelas,  metabolism  in,  315 

by   surra   trypanosoma,  metabo- 
lism in,  317 

mid-brain  and,  319 
infectious,  toxic  destruction  in,  323 
infective,  311 

insensible  perspiration  in,  320 
metabolism  in,  311 
milk  diet  in,  325 
muscular  work  and,  321 
neurogenic,  311,  315 
nitrogen    equilibrium   during,    328, 

329.  33? 
non-protein  diet  in,  163 
oxidation  in,  312 
parenchymatous    degeneration    in, 

33°. 
perspiration  in,  320 

physical  regulation  of  temperature 

in,  318,  320 
physiological,  311 
protein  diet  in,  high,  326 
purin  bases  in,  333 
rise  after  chill,  321 
sodium  chlorid  retention  in,  331 


Fever,  surgical  non-infective,  311 

sweat  elimination  in,  320 

toxic  processes  and,  313 

urea  output  in,  313 

uric  acid  elimination  in,  333,  346 

urine  in,  332 

water  elimination  in,  320 
retention  in,  331 
Fictitious  feeding,  147 
Flesh,  old  definition,  109 
Foods,  artificial,  108 

constitution  of,  early  study,  20 

definition,  107,  211 

energy  of,  growth  and,  248,  249 

heat  loss  in  warming,  91 

invalid,  value  of,  140 

patent,  value  of,  140 

protein,  influence  of,  107 

requirement  during  growth,  228 

statistics,  municipal,  222 

temperature   regulation    and,    ic6, 
217 

values  consumed  daily,  222 
Foodstuffs,  107 

caloric  value  of,  36 

definition,  107 

ideal,  107 

metabolism  of,  44 

ordinary,  composition,  366-374 

proper  proportion,  211 

specific  dynamic  action,   156,  361. 
See  also  Specific  dynamic  action. 
Forced  feeding  in  fever,  325 
Formaldehyde,     sugar      construction 

from,  277,  278 
Furs,  temperature  regulation  and,  105 


Galactose,  glycogen  from,  171 

Gastric  juice  in  starvation,  77 

Gelatin  in  starvation,  60 

influence  on  metabolism,  184 
sparing  action  of,  183 
specific  dynamic  action  of,  159,  160 
substituted    for    protein    in    mixed 

diet,  effect,  183 
value  of,  in  metabolism,  in 

Geometrically  similar  solids,  deter- 
mining surface  of,  88 

German  beer,  226 

Gliadin  ingestion,  influence  of,  on 
percent  of  glutamic  acid,  116,  117 

Globulin  increase  in  starvation,  78 

Glutamic  acid  in  blood-serum,  influ- 
ence of  ingestion  of  gliadin,  116, 
117 


INDEX   OF    SUBJECTS. 


393 


Glycocoll  in  organism,  123 

ingested    with    carbohydrates,    re- 
tention of,  123 
production    and   nitrogen  elimina- 
tion, constant  relation,  133 
from  protein,  133 
in  starvation,  71 
Glycogen  by  dehydration,  171 

complete   removal   by  tetanic  con- 
vulsions, 79,  172,  281 
distribution,  171,  172 
estimation,  171 
fatty  acid  from,  due  to  ascaris,  176, 

255 
freeing  organism  of,  79,  281 
from  dextrose,  171 
from  galactose,  171 
from  levulose,  171 
from  protein,  128 
from  protein  in  diabetes,   129 
in  starvation,  78 
metabolism  in  starvation,  64 

influence  on  protein  in  fasting,  56 
tetanus  to  free  organism  of,  79,  281 
Glycosuria,  alimentary,  272 

diabetes  and,  distinction    between, 

in  exophthalmic  goiter,  283 

phlorhizin,  272,  273 
Glycyl-glycin,  structure  of,  59 
Goiter,   exophthalmic,   glycosuria   in, 
283 
metabolism  in,  268 
Gout,  335,  350 

alcohol  and,  351 

diet  for,  356 

etiology,  35 1 

nucleo-protein  ingestion  in,  354 

Rontgen  rays  and,  355 

tolerance  for  purin  bodies  in,  355 

treatment,  356 

uric  acid  in  blood  and,  351 
retention  in,  354 
Graham  system  of  vegetarianism,  214 
Growth,  energy  of  ingested  food  and, 
248,  249 

fixed  tendency  towards,  249 

food  requirement  during,  228 

quota,  187,  188 
Guanase,  339 
Guanin,  335,  336 

metabolism  of,  343 


Hair,  temperature  regulation  and,  93 
Hard  workers,  diet  for,  221 


Heat,  animal,  32 

conduction  as  path  of  loss  of,  91 
elimination    in   starvation,    calcula- 
tion, 89 
estimated,  from  metabolism,  actual 

heat  and,  comparison,  42 
free,  from  proteins,  156,  361 
liberated  in  fasting,  39,  63 
loss  after  meat  ingestion,  distribu- 
tion, 154,  155 
by  radiation,  91 
by  warming  ingested  food,  91 

inspired  air,  91 
by  water  evaporation,  91 
fever  and,  316,  318 
paths  of,  91 

influence    of    temperature    on, 

97>  98,  99 
metabolism  and,  31,  32 
production  after  ingestion   of  pro- 
tein in  excess,  144,  146 
and  weight  in  starvation,  relation, 

64 
by  mother  and  offspring,   231 
in  first  hours  after  meat  diet,  133 
increase  in,  149 
with  constant  deposit  of  protein, 

151 
puncture  of  corpora  striata,  314 
requirement,  minimal,  153 
value  of  foodstuffs,  35,  36,  367.     See 
also  Caloric  value. 
of  metabolism,  35 
Hemoglobin  in  starvation,  78 
increase  at  high  altitudes,  266 
saturation  of,  with  oxygen,  262,  263 
Hepatic     disease,     carbohydrate     re- 
quirement in,  309 
High  altitudes,  diet  at,  264 
exercise  at,  263 
hemoglobin  increase  at,  266 
increase  of  red  corpuscles  at,  266 
metabolism  at,  258 
tolerance  for,  266 
Hippuric   acid   after   meat    ingestion, 

134,  13s 
in  urine,  135 

production  in  starvation,  71 
Homogentisic  acid  in  urine,   136 

output,  protein  metabolism  and, 
119 
Horseback  riding,  208 
Hospital  dietaries,  223 
Human  and  cow  milk,  relative  com- 
position, 241,  242 
calorimeter,  43 


394 


INDEX  OF  SUBJECTS. 


Humidity,  effect  on  metabolism  of  fat 
man,  103 

temperature  regulation  and,  96 
Hunger,  54.     See  also  Starvation. 

calcium,  54 

water,  54 
Hyperthermia,  311 
Hypertrophy,  muscular,  from  exercise, 

197 
Hypoxanthm,  335,  336 

in  muscle,  uric  acid  from,  349 


Ichthyosis        hystrix,      temperature 
changes  in,  312 

Infant,  breast-fed,  growth  in  grams  of, 
246,  247 
caloric  requirement  of,  246 
carbon  dioxid  output  of,  244 
metabolism  of,  243,  244,  245 
nutritive  requirement  of,  246 
respiratory  experiment  with,  244 
scientific  feeding  of,  246 

Infectious  fevers,  toxic  destruction  in, 

323 
Infective  fever,  311 
Insensible  perspiration,  amount  of,  17 

in  fever,  320 
Integral  factors  of  purin  metabolism, 

344,  345 
Intermediary  metabolism,  127,  128 

stage  of  protein  metabolism,  150 
Intermediate  metabolism,  133 
Intestinal  affections  in  children,  104 

mucosa  as  seat  of  deamination,  135, 
188 

work,  true,  absence  of,  147 
Intestines,   isolated  section,  excretion 

from,  48,  49 
Introduction,  17 
Invalid  foods,  value  of,  140 
Iron  in  milk,  240,  241 
Irreducible  minimum,  185 
Islands  of  Langerhans,  diabetes  and, 

304 
Isodynamic  law,  35 


Kyntjrenic  acid  in  urine,  137 

Laborers,  diet  for,  220 
Lactic  acid,  dextrose  from,  279 
from  dextrose,  308,  309 
in  urine  after  bloodletting,  256 
significance  of,  304,  306 


Lampblack,  effect  on  color  of  feces, 
46 

La  piqfire,  271,  272 

Law,  isodynamic,  35 

of  conservation  of  energy,  34 

of  constant  energy  expenditure,  250 

of  longevity,  251 

of  skin  area,  89,  90,  359 

Laws  governing  influence  of  tempera- 
ture on  metabolism,  153 

Legumes,  digestibility  of,  51 

Leukocythemia,  metabolism  in,  257 

Levulose,  glycogen  from,  171 

in  treatment  of  diabetes,  301,  302 

Levulosuria,  301 

Liebig's  extract  of  beef,  creatin  con- 
version in,  140 
value  of,  140 

Life,  length  of,  251 
in  starvation,  72 

Light  workers,  diet  for,  220 

Liver  diseases,  carbohydrate  require- 
ment, 180,  309 
in  oxidation  of  fatty  acids,  291,  292 
purin  bodies  and,  339 
urea-forming  function  of,  130 

Longevity,  law  of,  251 

Luxus  consumption,  213 


Maintenance  diet,  148 

requirement,  162 
March,  food  ration  for,  204 
Meat  and   fat   diet,  absence    of   sec- 
ondary rise  in  fat  metabolism 
on,  169 
secondary  rise  in  protein  me- 
tabolism on,  169 
and  rice  diet,  feces  from,  51,  52 
as  food,  108 

caloric  value  of,  126,  127 
commercial  preparations  of,   108 
diet,  exclusive,  no 

sulphur  and  phosphorus  elimina- 
tion, 141 
extracts,  food  value,  140 
increased,  after  nitrogen  equilibriimi, 

no 
ingestion,  heat  loss  after,  distribu- 
tion, i54,_  155 
production  in  first  hours,  133 
hippuric  acid  after,  134,  135 
hour-to-hour  metabolism  of,  119, 

120 
in   diabetes,   dextrose  and  nitro- 
gen elimination  in,  130 


INDEX   OF   SUBJECTS. 


395 


Meat  ingestion,  increased,  after  nitro- 
gen equilibrium,  no 
increasing  quantity  ingested,  no 
metabolism  after,  126 
uric  acid  elimination  and,  350 
powder  and  milli  in  fevers,  326 
specific  dynamic  action  of,  158 
Mechanical  energy,  34 

work,    atmospheric    pressure    and, 
260,  261 
by  fat  man,  193,  194 
carbohydrates  and,  201 
carbon   dioxid   output   and,    192, 
200,  202 
production  from,  elimination, 
202 
chemical  regulation  of  tempera- 
ture during,  92,  193 
conversion  of  fat  into  sugar  for, 

198,  199 
dynamic   equivalent  of,   metabo- 
lism and, 199 
effect  of  training,  68,  206 
energy  equivalents,  comparative, 

203,  204 
fats   and  carbohydrates  for,  rela- 
tive value,  198 
in  diabetes,  201 
influence  on  metabolism,  190 
nitrogen  metabolism  during,  194 
oxygen  absorption  during,  190 
protein  metabolism  during,   194, 

retention  during,  197 
specific   dynamic   action   during, 

192 
sugar  output  in  diabetes  and,  281 
urine  after,  196,  197 
water  excretion  during,   193 
Meconium,  47 
Mental    condition,    low   protein    diet 

and,  215 
Metabolism,  19 

after  ovariectomy,  267 
amount  of,  fever  and,  321 
and  heat  value,  44,  45 
at  high  altitudes,  258 
atmospheric  pressure  and,  259 
bloodletting  and,  255 
cane  sugar  and,  173 
carbohydrate,     d-glucuronic      acid 
and, 302 
ingestion  and,  171 
pentoses  and,  302 
castration  and,  267 
causes,  44,  359 


Metabolism,  clothes  and,  105 

cold  and,  91 

baths  and,  loi,  318 

definition,  19 

douches  and,  loi 

during  pregnancy,  230,  231 

dynamic  action  of,  42 

effect  of  oxygen  reduction  on,  253 
of  training  on,  68,  206,  207 

estimated    heat    from,    actual    heat 
and,  comparison,  42 

fat  ingestion  and,  165 

gelatin  in,  in 

glycogen,  in  starvation,  64 

influence  on  protein  in  fasting,  56 

heat  and,  31,  32 
value  of,  35 

body  area  and,  39 

in  anemia,  253 

in  diabetes,  271 
perverted,  295 

in  exophthalmic  goiter,  268 

in  fever,  311.     See  also  Fever.,  met- 
abolism in. 

in  leukocythemia,  257 

in  mountain  climbing,  205,  206 

in  myxedema,  268,  269 

in  phosphorus-poisoning,  271,  305 

in  pneumonia,  329,  330 

in  seven-day  fast,  65 

in    starvation,    25,    63.     See     also 
Starvation. 

in  youth,  170 

influence  of  alcohol  on,  225 
of  drugs,  358 
of  gelatin,  184 

intermediary,  127,  128,  133 

mechanical  work  and,  190 

nitrogen,  in  pregnancy,  233 

of  various  animals  in  starvation, 
61 

of  Cetti  in  starvation,  63 

of  child,  weight  and,  243 

of  fat  man,  humidity  influence,  103 
temperature  influence,  103 

of  foodstuffs,  44 

of  guanin,  343 

of  infant,  243,  244,  245 

of  obesity,  170,  267 

oxygen  requirement,  27,  28 

protein,  20.     See  also  Protein  metab- 
olism. 

purin,  335.     See  also  Purin  metab- 
olism. 

quantity  of,  359 

respiration  and,  30,  31 


396 


INDEX  OF   SUBJECTS. 


Metabolism,  speed  and,  205 
sunlight  and,  106,  260 
surface  area  and,  relation,  89 
temperature  and,  during  work,  92, 

193 
theory  of,  357 
thyroid  secretion  and,  267 
winds  and,  loi,  102 
Metric  and  avoirdupois  weights,  com- 
parison, 364 
Mid-brain,  induced  fever  and,  319 
Milk  and  meat  powder  in  fever,  326 
calcium  of,  241 
caloric  value,  241,  242,  243 
composition,   influence  of  diet  on, 
235.  236 
explanation,  238 
cow's,  dilution  of,  243 
diet,  224 

feces  from,  46 
in  fever,  325 
in  obesity,  225 
energy-constituents  of,  241 
fat  content  of,  diet  and,  236 
explanation,  239 
fasting  and,  236 
production  by  infiltration,  239 

from  protein,  235 
substitution  of    milk    sugar   for, 
248 
human   and  cow,   relative  composi- 
tion, 241,  242 
ingested  fat  in,  238 
iron  in,  240,  241 
production,  caloric  energy  and,  231, 

232_ 

nutrition  and,  235 
relation  of  growth  to  caloric  value 

of,  246,  247 
secretion  in  starvation,  77 
specific  adaptability  of,  240 
sugar  content,  diet  and,  236,  238 
heat  value,  41 
origin,  239 

substitution  of,  for  fat,  248 
top,  243 
Minimal  heat  requirement,  153 
Mono-amino-acid  fraction,  115 
Mothers,  nursing,  diet  for,  239 
Mountain  air,  benefits  of,  266 

climbing,  metabolism  in,  205,  206 
sickness,  263 
Municipal  food  statistics,  222 
Muscle,  resting,  uric  acid  in,  349 
Muscular  hypertrophy  from  exercise, 
197 


Muscular  work,  fever  and,  321 

protein  metabolism  and,  29 
Myxedema,  metabolism  in,  268,  269 


Nerves  in  temperature  regulation,  87 
Neurogenic  fever,  311,  315 
Nitrogen    and    dextrose    elimination, 
meat  ingestion  in  diabetes  and, 

130. 
ratio  in  diabetes,  131,  275,  283 

and  sulphur  output  in  starvation, 
67,  69 

assimilable,  45,  211 

balance  in  pregnancy,  232 

elimination,  121,  122 
after  breakfast,  121 
after    injection    of    serum    into 

bloodvessels,  58,  117 
and  dextrose  production  in  star- 
vation, ratio,  70 
in  prolonged  starvation,  66,  67 
temperature  and,  94,  100 
urea  production  as  index  to,  121 

equilibrium,  20,  108 
carbohydrates  and,  178 
carbon  equilibrium  and,  109 
during  fever,  328,  329,  330 
increased  meat  diet  after,  no 
low,  in  normal  nutrition,  181,  182 

in  undernutrition,  181,  182 
lowest  level,  212 

necessity    of    amino-acid    trypto- 
phan, 116 
on  protein-free  diet,  180 

fecal,  48,  49 

hunger,  specific,  180 

lag,  122,  124 

with  white  of  egg,  122 

metabolism  in  pregnancy,  233 

of  various  animals  in  starvation, 

61 
work  and,  194 

production    and    glycocoll    produc- 
tion, constant  relation,  133 

purin,  in  various  tissues,  348 

respiration  and,  21 

retention,  carbohydrates  and,  186 
fat  ingestion  and,  168 

skin  and,  22 

urinary,  as  measure  of  protein  de- 
struction, 20 
Nitrogenous  equilibrium,  20,  108 

urinary  constituents,  high  and  low 
protein  diets  and,  138 
Non-infective  surgical  fever,  311 


INDEX  OF   SUBJECTS. 


397 


Normal  diet,  210 

feces,  51,  52 
Nuclease,  342 
Nuclein  ingestion,  uric  acid  increase 

and,  33S 
Nucleoprotein  ingestion  in  gout,  354 

products  from,  337 
Nursing  mothers,  diet  for,  239 
Nutrition,  definition,  54 

historj'  of  science,  17 


Obesity,  170,  193,  194.  198 

diet  in,  182 

from  thjToid  deficiency,  267 

metabolism  of,  170,  267 

milk  diet  in   225 

thyroid  feeding  in,  268 
Octodecapeptid,  structure  of,  59 
Olive  oil,  heat  value,  40 
Ontogenetic  energy,  228 
Opium  in  diabetes,  300,  301 
Ordinary  foodstuffs,  composition,  366- 

374.      ,  .        ^ 

Organized  protem,  50 
Ovariectomy,  metabolism  after,  267 
Oxidation,  general,  reduced,  306 

within  body,  18,  19,  28 
Oxj'gen    absorption    during    exercise, 
190 
in  starvation,  62 
amount  absorbed,  18,  19 
needed,  28 

dependent  on  metabolism,  28 
and  carbon  dioxid  pressure  within 

alveoli,  262 
decrease  of,  dyspnea  from,  257 
importance  of,  18,  28,  30 
inhalations  in  fatigue,  254 
inspired,  and  carbon  dioxid  expired, 

relation,  23,  28,  30 
reduction,  effect  on  metabolism,  253 
requirement  during  pregnancy,  230 

in  metabolism,  27 
supply,    protein    metabolism    and, 

30.  31 

Pancreas  diabetes,  experimental,  272, 

274 
extirpation,  diabetes  and,  272,  274 
Parathyroidectomy,  temperature  after, 

270  .      •    r 

Parenchymatous  degeneration  in  lever, 

330 
Patent  foods,  value  of,  140 


Pentoses,     carbohydrate     metabolism 
and,  302 

diabetes  and,  302 

ehmination  of,  303 
Pentosuria,  303 
Peptids,  artificial,  59 
Perspiration  in  fever,  320 

in  temperature  regulation,  88 

insensible,  amount  of,  17 
in  fever,  320 
Phlorhizin  glycosuria,  272,  273 
Phosphoric  acid  output  in  starvation, 

67 
Phosphorus,  autolytic  action  of,  307 

elimination,  141 
Phosphorus-poisoning,  metabolism  in, 

Physical  power,  protein  diet  and,  197, 
198 
regulation  of  temperature,  88,  93 
Phvsiological  fever,  311 
Pneumonia,   metabolism  in,  329,  330 
Polypeptids,  59,  116 

as  constructive  nuclei  of  protein,  116 
Potassium  output  in  starvation,  69 
Potential  energ>%  34 
Predigested  foods,  113 
Pregnancy,  diet  in,  230 
energy  of,  229,  230 
metabolism  during,  230,  231 
nitrogen  balance  in,  232 
loss  in,  232 
metabolism,  233 
oxygen  requirement  during,   230 
protein  metabolism  before  and  after, 

233 
rise  in  nitrogen  output,  67 
Preparations  of  meat,  108 
Protein  and  fat  ingestion,  167,  168 
animal,  composition,  112 
breaking  up  into  amino-acids,  113, 

186 
caloric  value  of,  39 

source  of,  1 29 
carbon  retention  after,  144,  145 
circulating,  58,  60 
classification  according  to  rapidity 

of  destruction,  122 
composition  of,  113,  358 
content,  retention  of  ingested  pro- 
tein and, 187 
cost  and  energy,  table  of,  365 
cystin  elimination  and,  135 
deaminized  remainder  of,  129,  163 
denitrogenized    remainder   of,    129, 
163 


398 


INDEX  OF  SUBJECTS. 


Protein  deposit,  i86 

destruction,     urinary     nitrogen     as 

measure  of,  20 
diet,  exclusive,  109 

high  and  low,  nitrogenous  urin- 
ary constituents  and,  138 
in  fever,  326 
energy  value  of,  38,  163 
fat  production  from,  142 
food,  influence  of,  107 
foreign  to  body,  injections  of,  116, 

117 
free  heat  from,  156,  361 
gelatin    substituted    for,   in    mixed 

diet,  effect  of,  183 
glycogen  from,  128 

in  diabetes,  129 
heat  value  of,  36,  40 
in  excess,  heat  production  after,  144, 

146 
in  summer  diet,  restriction  of,  163 
influence  of  glycogen  metabolism  on, 

in  fasting,  56 
injections  of,  116,  117 
metabolism,  20 

abundant  nutrition  stage,  150 

after  bloodletting,  255 

apparatus  for  calculating,  22,  23, 
24 

appetite  as  signal,  218 

before  and  after  childbirth,  234 

before  and  after  pregnancy,  233 

carbohydrate     withdravi^al     and, 
179 

casein  injections  and,  117 

conditions  of,  189 

copious  vi^ater  drinking  and,  118 

day  and  night,  81 

dynamic  action,  186 

edestin  injections  and,  117 

endogenous,  139 

exogenous,  139 

external  temperature  and,  151 

fall  in,   from  carbohydrate  diet, 

173 
high,  213 

in  hot  weather,  217 
homogentisic  acid  output  and,  119 
in  diabetes,  160,  185,  186 
in  starvation,  61 

amount  of  fat  and,  72,  73 

fat  alone  in,  180,  181 
influence  of  diabetes  on,  284,  285 

of  fat  content  on,  in  starvation, 

75 
intermediary  stage,  150 


Protein  metabolism,  intermediate,  127, 
128 
low,    health    and    strength    and, 
212 
mental  condition  and,  215 
muscle  work  and,  29 
oxygen  supply  and,  30,  31 
secondary  dynamic  rise  on  meat- 
fat  diet,  169 
rise,  151 
stages  of,  150 
sugar  from,  132,  275 
temperature  and,  86 

influence,  laws  of,  153 
undernutrition  stage,  150 
urinary  nitrogen  as  measure  of,  20 
work  and,  29,  194,  195 
milk  fat  production  from,  235 
molecule,  early  cleavage  of,  128 
nitrogen,  assimilable,  45,  211 
of    blood-serum,    influence    of    in- 
gestion of  gliadin,  116,  117 
organized,  58 

origin  of  fat  from,  142,  304,  305 
oxidization  of,  108 
percentage  composition  of,  112,  113 
physical  power  and,  197,  198 
polypeptids    as    constructive  nuclei 

of,  116 
regeneration   of   amino-bodies  into, 

188 
respiratory  quotient  of,  28 

in  diabetes,  288 
retention  of,  during  work,  197 

protein  content  and,  187 
secondary  dynamic  action  of,  151 
specific  dynamic  action  of,  149,  158, 
159,  160 
in  diabetes,  281,  287,  288 
structure  of,  59 
superimposed    on    adequate    diet, 

metabolism  in,  122,  124 
synthesis  of,  within  organism,  114, 

116 
tissue  deposit  stage,  150 
vegetable,  composition  of,  112 
Proteolysis,  60,  113 
Proteolytic  cleavage  products,  60,  113 
Pulse-rate  in  starvation,  65 
Pure  deposit  of  tissue,  150 
Purin,  335 
bases,  336 

endogenous,  344 

source,  348 
exogenous,  344 
in  fever,  333 


INDEX  OF   SUBJECTS. 


399 


Purin  bodies,  336 

in  starvation,  68 

liver  and,  339 

relations  between,  335 

specific  capacity  for  burning,  343 

tolerance  of,  in  gout,  355 
metabolism,  335 

exercise  and,  349 

integral  factors  of,  344,  345 
nitrogen  in  various  tissues,  348 
Purin-free  diet,  344 

chemical    comparison    of    urines, 

.364 
Pyrimidin  bases,  337 


Racial   characteristics,   climate   and, 

104 
Radiation,  loss  of  heat  by,  91 
Rations  for  laborer,  211 

for  march,  calculation,  204 
Red  corpuscles,  increase  of,  at  high 

altitudes,  266 
Repair  quota,  185,  187,  188 
Respiration  and  metabolism,  30,  31 
apparatus,  22,  23,  24 
carbon    elimination    in,    from    in- 
gested meat,  126 
nitrogen  gas  and,  21 
Respiratory    experiment   with   infant, 
244 
quotient,  28,  64 

for  protein  in  diabetes,  288 

in  increased  meat  diet,  in 

of  egg,  229 

reduction  of,  after  exercise  at  high 

altitude,  263 
with      conversion     of     carbohy- 
drates into  fat,  176 
Resting  organism,  requirement  of,  219 
Rice  and  meat  diet,  feces  from,  51,  52 

diet,  feces  from,  51 
Rontgen  rays,  gout  and,  355 


Salmon,  metabolism  in,  58 
Scientific  feeding  of  infants,  246 
Secondary  dynamic  action  of  protein, 

151 
rise    in    fat    metabolism    on    meat- 
fat  diet,  absence  of,  169 
in  protein  metabolism,  151 
on  meat  fat  diet,  169 
Silicic  acid  diet,  effect  on  fecal  color,  47 
Skin  area,  law  of,  89,  90,  359 
nitrogen  excretion  and,  22 


Snake   venom,    swallowed,    immunity 

from,  118 
Sodium  chlorid  retention  in  fever,  331 

output  in  starvation,  69 
Soldiers  at  drill,  diet  for,  219,  220 
Somatose  as  food,  116 
Specific  d}Tiamic  action,  361 
during  work,  192 
of  amino-acids,  160 
of  cane  sugar,  160 
of  casein,  160 
of  fat,  158,  166 
of  foodstuffs,  156,  158 
cause,  163 
table,  157 
of  gelatin,  159,  160 
of  protein,  149,  158,  159,  160 

in  diabetes,  281,  287,  288 
of  sugar,  158 
nitrogen  hunger,  180 
Speed,  metabolism  and,  205 
Standard  dietaries,  222 

fuel  values,  41 
Starch,  heat  value,  of,  41 

particles  in  feces,  51 
Starvation,  54 

acetonuria  in,  69,  70 
albuminuria  in,  70 
ammonia  output  in,  68,  69 
beta-oxybutyric  acid  output  in,  69 
bile  flow  in,  77 
blood-plasma  in,  77,  78 
calcium  output  in,  67 
carbon  dioxid  elimination  in,  62 

night  and  day,  81,  82 
chlorin  output  in,  67,  68 
complete,  54 
creatin  output  in,  69 
day  and  night  metabolism,  81 
day  to  day  history,  56 
death  from,  74 

auto-intoxication  and,  76 
fat  content  and,  75 
dextrose  in,  77 

production   and   nitrogen   output 
in,  ratio,  70 
diabetes,  272 

effect  on  fat  content  of  milk,  236 
energy  requirements,  65 
fat  alone  in,  180,  181 
feces,  47 

functional  decrease  in,  77 
gastric  juice  in,  77 
gelatin  in,  60 
globulin  increase  in,  78 
glycocoll  production  in,  71 


400 


INDEX  OF  SUBJECTS. 


Starvation,  glycogen  in,  78 
metabolism  in,  64 
heat  elimination  in,  39,  40 

calculation,  89 
hemoglobin  in,  78 
hippuric  acid  production  in,  71 
influence    of    glycogen    metabolism 
on  protein  in,  56 
of  temperature  in,  94 
length  of  life  in,  72 
loss  in  weight  of  different  organs, 

76,  77 
metabolism  in,  25,  63 

effect  of  temperature  on,  100 

fat  and,  72,  73 

general  table,  65 

in  early  days,  66 

of  Cetti  in,  63 

protein,  61 
milk  secretion  in,  77 
nitrogen  and  sulphur  output  in,  67, 

metabolism  in,  61 
output  in,  67 

dextrose  production  and,  ratio, 
70 
organs  attacked  in,  76 
oxygen  absorption  in,  62 
phosphoric  acid  output  in,  67 
potassium  output  in,  69 
prolonged,  nitrogen  output  in,  66 
protein  metabolism  in,  61 
pulse-rate  in,  65 
purin  bodies  in,  68 
regularity  of,  119 
seven-day,  65 
sodium  output  in,  69 
sulphur  and  nitrogen  output  in,  67 
temperature  change  and,  82-85 

compared  with  carbon  dioxid 
elimination  in,  82-85 
urea  elimination  in,  influence  of  pre- 
vious diet,  57 
urine  in,  67,  68 
wear  and  tear  quota  in,  74 
weight  and  heat  production,  rela- 
tion, 64 
loss  in,  73 
work  and,  79 
Subcutaneous  fat,  temperature  regu- 
lation and,  93, 95 
Suckling  pigs,  growth  of,  247 
Sugar,  carbon  dioxid  output  and,  176, 
177 
cornbustion,  lessened,  fatty  infiltra- 
tion from,  257,  304 


Sugar,    construction    from    formalde- 
hyde, 277,  278 
effect  on  feces,  48 
from  protein  metabolism,  132,  275 
heat  value,  41 
producers,  279,  280 
specific  dynamic  action  of,  158 
Sulphur  and  nitrogen  output  in  starva- 
tion, 67,  69 
elimination,  141 
rapidity  of,  122 
Summer  complaint  in  New  York,  104 

diet,  217 
Sunlight,  metabolism  and,  106,  260 
Sun's  energy,  34 
Sunstroke,  311 

Surface  and  weight,  relation,  88,  89 
area,  determining,  88 
heat  value  and,  39 
metabolism  and,  relation,  89 
of    geometrically    similar    solids, 
determining,  88 
Surgical  fever,  non-infective,  311 
Surra  trypanosomas,  fever  induced  by, 

metabolism  in,  317 
Sweat  elimination  in  fever,  320 

temperature  and,  88 
Swimming,  208 


Taurin  of  bile,  cystin  and,  136 
Tea,  recuperative  power  of,  202 
Temperature  after  parathyroidectomy, 
270 
change  compared  with  carbon   di- 
oxid elimination  in  starvation, 
82-85 
in  ichthyosis  hystrix,  312 
starvation  and,  82-85 
effect  on  metabolism  in  starvation, 
100 
of  fat  man,  103 
on  nitrogen  elimination,  100 
external,   protein   metabolism  and, 

151 
humidity,  and  work,  effect  on  fat 

man,  193,  194 
influence  of,  on  manner  of  heat  loss, 

97.  98,  99 
metabolism  and,  86 

during  work,  92,  193 
nitrogen  elimination  and,  94 
protein  metabolism  and,  laws,  153 
regulation  of,  86 

chemical,  88,  92,  99 
during  work,  92,  193 


INDEX   OF   SUBJECTS. 


401 


Temperature,    regulation    of,    clothes 
in,  104 
cutaneous  blood  supply  and,  88 
external  cold  and,  88 
food  and,  106,  217 
furs  and,  105 
hair  and,  93 

influence  on  starvation,  94 
humidity  and,  96 
nerves  in,  87 
perspiration  in,  88 
physical,  88,  93 

in  fever,  318,  320 
subcutaneous  fat  and,  93,  95 
sweat  and,  88 
Test-diet  in  diabetes,  298 
Tetanus  to  free  organism  of  glycogen, 

79,  172,  281 
Tetany  after   parathyroidectomy,  270 
Theobald  Smith  phenomenon,  118 
Thermometer  showing  comparison  of 

Fahrenheit  and  centigrade,  363 
Thirst,  54 

Thyroid  gland,  diabetes  and,  283 
in  obesity,  268 

secretion,  metabolism  and,  267 
obesity  and,  267 
Thyroiodin,  267 

Tissue,  constitution  of,  early  study,  20 
crushed,  uric  acid  destruction  and, 

340,  341 
protein  deposit  stage,  150 
Top  milk,  243 

Training,   efifect   on    metabolism,    68, 
206,  207 
mechanical  work  accomplished  and, 
68,  206 
Tryptophan  an  essential  to  nitrogen 
equilibrium,  116 
kynurenic  acid  and,  137,  138 
Tuberculosis,  fever  in,  323 
Typhoid     fever,     high     carbohydrate 
diet  in,  327-329 
protein  diet  in,  326 


Undeknutrition,  low  nitrogen  equi- 
librium in,  181,  182 
stage  of  protein  metabolism,  150 
Urea  elimination  in  fever,  313 

in  starvation,  influence  of  previous 
diet,  57 
from  uric  arid  per  os,  342 
production   as  index   of   exogenous 
protein  metabolism,  138 
Uric  acid,  33-;,  336 

26 


Uric  acid  and  allantoin,  relation,  342 
destruction,   crushed  tissue    and, 

340,  341 
elimination,    constancy    of,    344, 

345 
m  fever,  333,  346 

endogenous,  344 

exogenous,  344 

in  blood,  gout  and,  351 

in  resting  muscle,  349 

increase,    nuclein    ingestion    and, 
338 

meat  ingestion  and,  350 

per  OS,  342 

production  of,  338 

retention  in  gout,  354 
Urine,  caloric  value  of,  37 

character  of,  after  work,  196,  197 
chemical  comparison  of,  on  purin- 

free  diets,  364 
constitution  of,  early  study,  20 
creatin  in,  138 
creatinin  in,  138 
cystin  in,  135 
hippuric  acid  in,  135 
homogentisic  acid  in,  136 
in  fever,  332 
in  starvation,  67,  68 
kynurenic  acid  in,  136 
lactic  acid  in,  after  bloodletting,  256 
nitrogen  in,  as  measure  of  protein 

destruction,  20 
uroleucinic  acid  in,  136 
Urolcucinic  acid  in  urine,  136 


Vegetables,  digestibility  of,  51,  53 

proteins,  composition  of,  112 
Vegetarianism,  Graham  system,  214 
Venom,  snake,  swallowed,  immunity 
from,  118 


Warm-bi.ooded  animals,  heat  libera- 
tion of,  40 
Warming  ingested  food,  heat  loss  by, 

inspired  air,  heat  loss  by,  91 
Water  drinking,  copious,  protein  met- 
abolism and,  118 

elimination  during  work,  193 
in  fever,  320 

evaporation  as  refrigerating  factor, 

154 
heat  loss  by,  91 
hunger,  54 


402 


INDEX   OF   SUBJECTS. 


Water  retention  in  fever,  331 
Wear  and  tear  quota,  74,  185,  186 

in  starvation,  74 
Weight  and  heat  production  in  starva- 
tion, relation,  64 
and  surface,  relation,  88,  89 
influence  on   metabolism  of  child, 

243 
loss  in  starvation,  73 
White  of  egg,  nitrogen  lag  with,  122 


Winds,  metabolism  and,  loi,  102 
Work,   mechanical,   metabolism  and, 
190 

starvation  and,  79 

Xanthin,  335,  336 
oxidazes,  338 

Youth,  metabolism  in,  170 


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Myomata  of  the  Uterus.  By  Howard  A.  Kelly,  M.  D.,  Professor 
of  Gynecologic  Surgery  at  Johns  Hopkins  University;  and  Thomas  S. 
CuLLEN,  M.  B.,  Associate  in  Gynecology  at  Johns  Hopkins  University. 
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' '  We  started  off  without  any  preconceived  theories  and  determined  carefully 
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GYNECOLOGY  AND    OBSTETRICS 


Cullen's 
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Adenomyoma  of  the  Uterus.  By  Thomas  S.  Cullen,  M.  D., 
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The  Lancet,  London 

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GiAECOLOGV  AND    OBSTETRICS 


Bandler*s 
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Medical  Gynecology.  By  S.  Wvllis  Bandler,  M.  D.,  Adjunct 
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EXCLUSIVELY     MEDICAL    GYNECOLOGY 

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Americeoi  Journal  of  Obstetrics 

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Kelly  and   Noble's 

Gynecology 

and  Abdominal  Surgery 


Gynecology  and  Abdominal  Surgery.  Edited  by  Howard  A. 
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for  the  physician  engaged  in  general  practice.  Heretofore  the  general  practitioner 
was  compelled  to  search  through  an  entire  work  in  order  to  obtain  the  information 
desired.  Abdominal  surgery  proper,  as  distinct  from  gynecology,  is  fully  treated, 
embracing  operations  upon  the  stomach,  upon  the  intestines,  upon  the  liver  and 
bile-ducts,  upon  the  pancreas  and  spleen,  upon  the  kidneys,  ureter,  bladder,  and 
the  peritoneum.  The  illustrations  are  truly  magnificent,  being  the  work  of  Mr. 
Hermarm  Becker  and  Mr.  Max  Br'ddel. 

American  Journal  of  the  Medical  Sciences 

"  It  is  needless  to  say  that  the  work  has  been  thoroughly  done  :  the  names  of  the  authors 
and  editors  would  guarantee  this ;  but  much  may  be  said  in  praise  of  the  method  of  presen- 
tation, and  attention  may  be  called  to  the  inclusion  of  matter  not  to  be  found  elsewhere." 


GYNECOLOGY  AND   OBSTETRICS 


Webster's 
Text-Book  qf  Obstetrics 

A  Text=Book  of  Obstetrics.  B\'  J.  Clarence  Webster,  M.  D. 
(Edin.),  F.  R.  C.  p.  E.,  Professor  of  Obstetrics  and  Gynecology  in  Rush 
Medical  College,  in  affiliation  with  the  University  of  Chicago.  Octavo 
volume  of  767  pages,  illustrated.  Cloth,  ^5.00  net;  Half  Morocco, 
$6.50  net. 

BEAUTIFULLY     ILLUSTRATED 

In  this  work  the  anatomic  changes  accompanying  pregnancy,  labor,  and  the 
puerperium  are  described  more  fully  and  lucidly  than  in  any  other  text-book  on 
the  subject.  The  exposition  of  these  sections  is  based  mainly  upon  studies  of 
frozen  specimens.  Unusual  consideration  is  given  to  embryologic  and  physiologic 
data  of  importance  in  their  relation  to  obstetrics. 

Buffalo  Medical  Journal 

"  As  a  practical  text-book  on  obstetrics  for  both  student  and  practitioner,  there  is  left  very 
little  to  be  desired,  it  being  as  near  perfection  as  any  compact  work  that  has  been  published." 


Webster's 
Diseases   of  Women 

A  Text-Book  of  Diseases  of  Women.  By  J.  Clarence  Webster, 
M.  D.  (Edin.),  Y.  R.  C.  P.  E.,  Professor  of  Gynecology  and  Obstetrics 
in  Rush  Medical  College.  Octavo  of  712  pages,  with  372  text-illustra- 
tions and  10  colored  plates.     Cloth,  $7.00  net ;  Half  Morocco,  $8.50  net. 

Dr.  Webster  has  written  this  work  especially  for  the  general  practitioner,  dis- 
cussing the  clinical  features  of  the  subject  in  their  widest  relations  to  general 
practice  rather  than  from  the  standpoint  of  specialism.  The  magnificent  illus- 
trations, three  hundred  and  seventy-two  in  number,  are  nearly  all  original. 

Howard  A.  Kelly.  M.  D., 

Professor  of  (iytiecology.  Johns  Hopkins  Univrrsity. 

"  It  is  undoubtPfliy  one  of  the  best  works  whicli  has  been  put  on  tiic  market  within  recent 
years,  .showing  from  start  to  finish  Dr.  Webster's  well-known  thoroughness.  The  illustrations 
are  also  of  the  hit'hcst  order." 


SAUNDERS'   BOOKS   ON 


Hirst's 
Text-Book  of  Obstetrics 

Just  Ready— The  New  (6th)  Edition 


A  Text=Book  of  Obstetrics.  By  Barton  Cooke  Hirst,  M.  D., 
Professor  of  Obstetrics  in  the  University  of  Pennsylvania.  Handsome 
octavo,  915  pages,  with  767  illustrations,  40  of  them  in  colors.  Cloth, 
^5.00  net;  Sheep  or  Half  Morocco,  ;^6.50  net. 

WITH    767    ORIGINAL    ILLUSTRATIONS 

Immediately  on  its  publication  this  work  took  its  place  as  the  leading  text-book 
on  the  subject.  Both  in  this  country  and  in  England  it  is  recognized  as  the  most 
satisfactorily  written  and  clearly  illustrated  work  on  obstetrics  in  the  language. 
The  illustrations  form  one  of  the  features  of  the  book.  They  are  numerous  and 
the  most  of  them  are  original.  In  this  edition  the  book  has  been  thoroughly  revised. 
More  attention  has  been  given  to  the  diseases  of  the  genital  organs  associated  with 
or  following  childbirth.  Many  of  the  old  illustrations  have  been  replaced  by  better 
ones,  and  there  have  been  added  a  number  entirely  new.  The  work  treats  the 
subject  from  a  clinical  standpoint. 


OPINIONS  OF  THE  MEDICAL  PRESS 


British  Medical  Journal 

"  The  popularity  of  American  text-books  in  this  country  is  one  of  the  features  of  recent 
years.  The  popularity  is  probably  chiefly  due  to  the  great  superiority  of  their  illustrations 
over  those  of  the  English  text-books.  The  illustrations  in  Dr.  Hirst's  volume  are  far  more 
numerous  and  far  better  executed,  and  therefore  more  instructive,  than  those  commonly 
found  in  the  works  of  writers  on  obstetrics  in  our  own  country." 

Bulletin  of  Johns  Hopkins  Hospital 

"The  work  is  an  admirable  one  in  every  sense  of  the  word,  concisely  but  comprehensively 
written." 

The  Medical  Record,  New  York 

"The  illustrations  are  numerous  and  are  works  of  art,  many  of  them  appearing  for  the  first 
time.  The  author's  style,  though  condensed,  is  singularly  clear,  so  that  it  is  never  necessary 
to  re-read  a  sentence  in  order  to  grasp  the  meaning.  As  a  true  model  of  what  a  modern  text- 
book on  obstetrics  should  be,  we  feel  justified  in  affirming  that  Dr.  Hirst's  book  is  without  a 
rival." 


DISEASES    OF    WOMEN. 


HirstV 
Diseases  of  Women 


A  Text=Book  of  Diseases  of  Women.  By  Barton  Cooke  Hirst, 
M.  D.,  Professor  of  Obstetrics,  University  of  Pennsylvania  ;  Gynecolo- 
gist to  the  Howard,  the  Orthopedic,  and  the  Philadelphia  Hospitals. 
Octavo  of  745  pages,  with  701   original  illustrations,  many  in  colors. 

Cloth,  $5.00  net;  Half  Morocco,  ^6.50  net. 

THE    NEW   (2d)    EDITION 
WITH    701    ORIGINAL    ILLUSTRATIONS 

The  new  edition  of  this  work  has  just  been  issued  after  a  careful  revision. 
As  diagnosis  and  treatment  are  of  the  greatest  importance  in  considering  diseases 
of  women,  particular  attention  has  been  devoted  to  these  divisions.  To  this  end, 
also,  the  work  has  been  magnificently  illuminated  with  701  illustrations,  for  the 
most  part  original  photographs  and  water-colors  of  actual  clinical  cases  accumu- 
lated during  the  past  fifteen  years.  The  palliative  treatment,  as  well  as  the 
radical  operative,  is  fully  described,  enabling  the  general  practitioner  to  treat 
many  of  his  own  patients  v  iihout  referring  them  to  a  specialist.  An  entire  sec- 
tion is  devoted  to  r  full  description  of  all  modern  gynecologic  operations,  illumi- 
nated and  elucidac3J  by  numerous  photographs.  The  author's  extensive  ex- 
perience renders  i.nis  work  of  unusual  value. 


OPINIONS  OF  THE  MEDICAL  PRESS 


Medical  Record,  New  York 

"  Its  merits  can  be  appreciated  only  by  a  careful  perusal.  .  .  .  Nearly  one  hundred  pages 
are  devoted  to  technic,  this  chapter  being  in  some  respects  superior  to  the  descriptions  in 
many  other  text-  boks." 

Boston  Medical  and  Surgical  Journal 

"The  author  has  given  special  attention  to  diagnosis  and  treatment  throughout  the  book, 
and  has  produced  a  practical  treatise  which  should  be  of  the  greatest  value  to  the  student,  the 
general  practitioner,  and  the  specialist." 

Medical  Newi,  New  York 

"  ( ;ffi' <•  tr<Mtiri<-nt  is  given  a  due  amount  of  consideration,  so  that  the  work  will  be  as 
useful  to  the  non-operator  as  to  the  specialist." 


SAUNDERS'    BOOKS   ON 


GET  i^ •  THE  NEW 

THE  BEST  /\  m  6  r  1  C  Si  n         standard 


American 
Illustrated   Dictionary 

Just  Ready— The   New  (5th)  Edition 


The  American  Illustrated  Medical  Dictionary.  A  new  and  com- 
plete dictionary  of  the  terms  used  in  Medicine,  Surgery,  Dentistry, 
Pharmacy,  Chemistiy,  and  kindred  branches;  with  over  lOO  new  and 
elaborate  tables  and  many  handsome  illustrations.  By  W.  A.  Newman 
Borland,  M.  D.,  Editor  of  "  The  American  Pocket  Medical  Diction- 
ary." Large  octavo,  nearly  8/6  pages,  bound  in  full  flexible  leather. 
Price,  ^4.50  net;  with  thumb  index,  $5.00  net. 

Gives  a  Meudmum  Amount  of  Matter  in  a  Minimum  Space,  and  at  the  Lowest 

Possible  Cost 

WITH  2000  NEW  TERMS 

The  immediate  success  of  this  work  is  due  to  the  special  features  that  distin- 
guish it  from  other  books  of  its  kind.  It  gives  a  maximum  of  matter  in  a  mini- 
mum space  and  at  the  lowest  possible  cost.  Though  it  is  practically  unabridged, 
yet  by  the  use  of  thin  bible  paper  and  flexible  morocco  binding  it  is  only  1 3^ 
inches  thick.  The  result  is  a  truly  luxurious  specimen  of  book-making.  In  this 
new  edition  the  book  has  been  thoroughly  revised,  and  upward  of  fifteen  hundred 
new  terms  that  have  appeared  in  recent  medical  literature  have  been  added,  thus 
bringing  the  book  absolutely  up  to  date.  The  book  contains  hundreds  of  terms 
not  to  be  found  in  any  other  dictionary,  over  loo  original  tables,  and  many  hand- 
some illustrations,  a  number  in  colors. 


PERSONAL    OPINIONS 


Howard  A.  Kelly,  M.  D., 

Professor  of  Gynecology,  Johns  Hopkins  University,  Baltimore. 

"  Dr.  Borland's  dictionary  is  admirable.     It  is  so  well  gotten  up  and  of  such  convenient 
size.     No  errors  have  been  found  in  my  use  of  it." 

J.  Collins  Warren,  M.D.,  LL.D.,  F.R.C.S.  (Hon.) 

Professor  of  Surgery^  Harvard  Medical  School. 

"  I  regard  it  as  a  valuable  aid  to  my  medical  literary  work.     It  is  very  complete  and  of 
conTenient  size  to  handle  comfortably.     I  use  it  in  preference  to  any  other. ' ' 


GYNECOLOGY  AND    OBSTETRICS 


Penrose's 
Diseases  of  Women 

Sixth    Revised    Edition 


A  Text-Book  of  Diseases  of  Women.  By  Charles  B.  Penrose, 
M.  D.,  Ph.  D.,  formerly  Professor  of  Gynecology  in  the  University  of 
Pennsylvania ;  Surgeon  to  the  Gynecean  Hospital,  Philadelphia.  Oc- 
tavo volume  of  550  pages,  with  225  fine  original  illustrations.     Cloth, 

;g3.75   net. 

RECENTLY    ISSUED 

Regularly  every  year  a  new  edition  of  this  excellent  text-book  is  called  for, 
and  it  appears  to  be  in  as  great  favor  with  physicians  as  with  students.  Indeed, 
this  book  has  taken  its  place  as  the  ideal  work  for  the  general  practitioner.  The 
author  presents  the  best  teaching  of  modern  gynecology,  untrammeled  by  anti- 
quated ideas  and  methods.  In  every  case  the  most  modern  and  progressive 
technique  is  adopted,  and  the  main  points  are  made  clear  by  excellent  illustra- 
tions. The  new  edition  has  been  carefully  revised,  much  new  matter  has  been 
added,  and  a  number  of  new  original  illustrations  have  been  introduced.  In  its 
revised  form  this  volume  continues  to  be  an  admirable  exposition  of  the  present 
status  of  gynecologic  practice. 


PERSONAL  AND   PRESS  OPINIONS 


Howard  A.  Kelly,  M.  D., 

Professor  of  Gynecology  and  Obstetrics,  Johns  Hopkins  University,  Baltimore. 
••  I  shall  value  very  highly  the  copy  of  Penrose's  '  Diseases  of  Women  '  received.     I  have 
already  recommended  it  to  my  class  as  THE  BEST  book." 

E.  E.  Montgomery,  M.  D., 

Professor  of  Gynecology,  Jefferson  Medical  College.  Philadelphia. 
"  The  copy  of '  A  Text-Book  of  Diseases  of  Women  '  by  Penrose,  received  to-day.     I  have 
looked  over  it  and  admire  it  very  much.     I  have  no  doubt  it  will  have  a  large  sale,  as  it  justly 
merits.  " 

Bristol  Medico-Chirur^icaJ  Journal 

••  -I  his  is  an  .xr.-ll-nt  work  which  goes  straight  to  the  mark The  book  may  be  taken 

as  a  trustworthy  exposition  of  modern  gynecology." 


11  SAUNDERS'    BOOKS   ON 

Dorland's 
Modern  Obstetric./* 


Modern  Obstetrics :  General  and  Operative.  By  W.  A.  Newman 
Borland,  A.  M.,  M.  D.,  Assistant  Instructor  in  Obstetrics,  Univer- 
sity of  Pennsylvania;  Associate  in  Gynecology  in  the  Philadelphia 
Polyclinic.  Handsome  octavo  volume  of  797  pages,  with  201  illustra- 
tions.    Cloth,  ^4.00  net. 

Second  Edition,  Revised  and  Greatly  Enlarged 

In  this  edition  the  book  has  been  entirely  rewritten  and  very  greatly  enlarged. 
Among  the  new  subjects  introduced  are  the  surgical  treatment  of  puerperal  sepsis, 
infant  mortality,  placental  transmission  of  diseases,  serum-therapy  of  puerperal 
sepsis,  etc.  By  new  illustrations  the  text  has  been  elucidated,  and  the  subject  pre- 
sented in  a  most  instructive  and  acceptable  form. 

Journal  of  the  American  Medical  Association 

"  This  work  deserves  commendation,  and  that  it  has  received  what  it  deserves  at  the  hands 
of  the  profession  is  attested  by  the  fact  that  a  second  edition  is  called  for  within  such  a  short 
time.     Especially  deserving  of  praise  is  the  chapter  on  puerperal  sepsis." 

Davis'  Obstetric  and 
Gynecologic  Nursing 

Obstetric  and  Gynecologic  Nursing.    By  Edward  P.  Davis,  A.  M., 
M.  D.,  Professor   of  Obstetrics    in   the  Jefferson  Medical   College  and 
Philadelphia   Polyclinic ;    Obstetrician    and    Gynecologist,   Philadelphia 
Hospital.     i2mo  of  436  pages,  illustrated.     Buckram,  ^1.75  net. 
THE     NEW    (3d)    EDITION 

Obstetric  nursing  demands  some  knowledge  of  natural  pregnancy,  and  gyne- 
cologic nursing,  really  a  branch  of  surgical  nursing,  requires  special  instruction 
and  training.  This  volume  presents  this  information  in  the  most  convenient 
form.  This  third  edition  has  been  very  carefully  revised  throughout,  bringing  the 
subject  down  to  date. 

The  Lancet,  London 

"  Not  only  nurses,  but  even  newly  qualified  medical  men,  would  learn  a  great  deal  by  a 
perusal  of  this  book.  It  is  written  in  a  clear  and  pleasant  style,  and  is  a  work  we  can  recom- 
mend." 


GYNECOLOGY  AND    OBSTETRICS. 


Garrigues* 
Diseases  of  Women 

Third  Edition,  Thoroughly  Revised 


A  Text-Book  of  Diseases  of  Women.  By  Henry  J.  Garrigues, 
A.  M.,  M.  D.,  Gynecologist  to  St.  Mark's  Hospital  and  to  the  German 
Dispensary,  New  York  City.  Handsome  octavo,  756  pages,  with  367 
engravings  and  colored  plates.  Cloth,  $df.^Q>  net;  Sheep  or  Half 
Morocco,  ;^6.oo  net. 

The  first  two  editions  of  this  work  met  with  a  most  appreciative  reception  by 
the  medical  profession  both  in  this  country  and  abroad.  In  this  edition  '.he  entire 
work  has  been  carefully  and  thoroughly  revised,  and  considerable  new  matter 
added,  bringing  the  work  precisely  down  to  date.  Many  new  illustrations  have  been 
introduced,  thus  greatly  increasing  the  value  of  the  book  both  as  a  text-book  and 
book  of  reference. 

Thad.  A.  Reamy,  M.  D. ,   Professor  of  Clinical  Gynecology,  Medical  College  of  Ohio. 

'One  of  the  best  text-books  for  students  and  practitioners  which  has  been  publislied  in  the 
English  language  ;  it  is  condensed,  clear,  and  comprehensive.  The  profound  learning  and 
great  clinical  experience  of  the  distinguished  author  find  expression  in  this  book." 


American  Text-Book  cf  Gynecology 

Second    Revised    Edition 
*  American    Text-Book  of   Gynecology.     Edited    by  J.    M.    Baldv, 
M.  D.     Imperial  octavo  of  718  pages,  with  341    text-illustrations  and 
38  plates.     Cloth,  |;6.oo  net. 

American  Text-Book  cf  Obstetrics 

Second    Revised    Edition 
The  American  Text-Book  of  Obstetrics.     In  two  volumes.    Edited 
by  Richard  C.  Ncjkki.s,  M.  \). ;  Art  l':<litor,  Robert  L.  Dickinson,  M.  D. 
Two  octavos  of  about  600  pages  each  ;  nearly  900  illustrations,  includ- 
ing 49  colored  and  half-tone  plates.      Per  volume  :  Cloth.  $3.50  net. 

"  As  an  aiilhorily,  as  a  Ixjok  of  reference,  as  a  '  working  book  '  for  the  student  or  piacli- 
tioner.  we  commend  it  because  we  believe  there  is  no  belter."— Amkkican  Journal  ov  TilK 

MEUICAI.    SclfcNCh-S. 


14  SAUNDERS'    BOOKS   ON 

Schaffer  and  Edgar's  Labor  and  Operative  Obstetrics 

Atlas  and   Epitome  of    Labor    and    Operative   Obstetrics.      By   Dr. 

O.  ScHAFFER,  of  Heidelberg.  Edited,  with  additions,  by  J.  Clifton  Edgar, 
M.  D.,  Professor  of  Obstetrics  and  Clinical  Midwifery,  Cornell  University 
Medical  School,  New  York.  With  14  lithographic  plates  in  colors,  139  text- 
cuts,  and  III  pages  of  text.     Cloth,  $2.00  net.     In  Saunders'  Hand-Atlases. 

American  Medicine 

"  It  would  be  difficult  to  find  one  hundred  pages  in  better  form  or  containing  more 
practical  points  for  students  or  practitioners." 

Schaffer     and     Edgar's     Obstetric     Diag'nosis     and 
Treatment 

Atlas  and  Epitome  of  Obstetric  Diagnosis  and   Treatment.    By  Dr. 

O.  Schaffer,  of  Heidelberg.  Edited,  with  additions,  by  J.  Clifton  Edgar, 
M.  D.,  Professor  of  Obstetrics  and  Clinical  Midwifery,  Cornell  University 
Medical  School,  New  York.  With  122  colored  figures  on  56  plates,  38  text- 
cuts,  and  315  pages  of  text.      Cloth,   ^3.00  net.      Saunders'  Hand- Atlases. 

New  York  Medical  Journal 

"The  illustrations  are  admirably  executed,  as  they  are  in  all  of  these  atlases,  and  the  text 
can  safely  be  commended." 

Schaffer  and  Norris*  Gynecolo^ 

Atlas  and  Epitome  of  Gynecology.  By  Dr.  O.  Schaffer,  of  Heidel- 
berg. Edited,  with  additions,  by  Richard  C.  Norris,  A.  M.,  M.  D., 
Gynecologist  to  Methodist  Episcopal  and  Philadelphia  Hospitals.  With  207 
colored  figures  on  90  plates,  65  text-cuts,  and  308  pages  of  text.  Cloth, 
^^3.50  net.      In  Sauttders'  Hand-Atlas  Series. 

American  Journal  of  the  Medical  Sciences 

"  Of  the  illustrations  it  is  difficult  to  speak  in  too  high  terms  of  approval.  They  are  so 
clear  and  true  to  nature  that  the  accompanying  explanations  are  almost  superfluous." 

Galbraith's  Four  Epochs  of  Woman's   Life 

New  (2d)  Edition 

The  Four  Epochs  of  Woman's  Life :  A  Study  in  Hygiene.  By  Anna 
M.  Galbraith,  M.  D.,  Fellow  of  the  New  York  Academy  of  Medicine,  etc. 
With  an  Introductory  Note  by  John  H.  Musser,  M.  D.,  University  of 
Pennsylvania.      i2mo  of  247  pages.      Cloth,  $1.50  net. 

Birming'ham  Medical  Review,  England 

"  We  do  not,  as  a  rule,  care  for  medical  books  written  for  the  instruction  of  the  pubHc. 
But  we  must  admit  that  the  advice  in  Dr.  Galbraith's  work  is,  in  the  main,  wise  and 
wholesome." 


G  YNECOLOG  V  AND    OBSTE TRICS.  1 5 


Schaffer  and  Webster's 
Operative  Gynecology 


Atlas  and  Epitome  of  Operative  Gynecology.  By  Dr.  O.  Schaf- 
fer, of  Heidelberg.  Edited,  with  additions,  by  J.  Clarence  Webster, 
M.D.  (Edin.),  F.R.C.P.E.,  Professor  of  Obstetrics  and  Gynecology  in 
Rush  Medical  College,  in  affiliation  with  the  University  of  Chicago. 
42  colored  lithographic  plates,  many  text-cuts,  a  number  in  colors,  and 
138  pages  of  text.     ///  Smmders  Hand- Atlas  Scries.    Cloth,  $3.00  net. 


Much  patient  endeavor  has  been  expended  by  the  author,  the  artist,  and  the 
lithographer  in  the  preparation  of  the  plates  of  this  atlas.  They  are  based  on 
hundreds  of  photographs  taken  from  nature,  and  illustrate  most  faithfully  the 
various  surgical  situations.  Dr.  Schaffer  has  made  a  specialty  of  demonstrating 
by  illustrations. 

Medical  Record,  New  York 

•'  The  volume  should  prove  most  helpful  to  students  and  others  in  grasping  details  usually 
to  be  acquired  only  in  the  amphitheater  itself."  ^^^^^^^^^^^ 

De  Lee's 
Obstetrics  for  Nurses 

Obstetrics  for  Nurses.  By  Joseph  B.  De  Lee,  M.D.,  Professor  of 
Obstetrics  in  the  Northwestern  University  Medical  School ;  Lecturer 
in  the  Nurses'  Training  Schools  of  Mercy,  Wesley,  Provident,  Cook 
County,  and  Chicago  Lying-in  Hospitals.  1 2mo  volume  of  5 1 2  pages, 
fully  illustrated.  Cloth.  $2.50  net. 

THE  NEW  (3d)  EDITION 
While  I)r  De  Lee  has  written  his  work  especially  for  nurses,  yet  the  prac- 
titioner will  find  it  useful  and  instructive,  since  the  duties  of  a  nurse  often  devolve 
upon  him  in  the  early  years  of  his  practice.  The  illustrations  are  nearly  all 
original  and  represent  photographs  taken  from  actual  scenes.  1  he  text  is  the 
result  of  the  author's  many  years'  experience  in  lecturing  to  the  nurses  of  five 
different  training  schools. 

J.  Clifton  Edgar.  M.  D..  ,      -r      v    / 

Professor  of  Obstetrics  and  Cltnual  Midwifery.  Cornell  U,nvers,tv .  New  \  orK. 
"  It  is  far  and  away  the  best  that  h..s  come  to  my  notice,  and  I  shall  take  great  pleasure  in 
recommending  it  to  my  nurses,  and  students  as  well." 


i6     SAUNDERS'  BOOKS  ON  GYNECOLOGY  AND  OBSTETRICS. 


American  Pocket  Dictionary  ^^*^  """"tust^iS 

The  American  Pocket  Medical  Dictionary.  Edited  by  W. 
A.  Newman  Borland,  A.  M.,  M.  D.,  Assistant  Obstetrician  to  the 
Hospital  of  the  University  of  Pennsylvania ;  Fellow  of  the  American 
Academy  of  Medicine.  Over  598  pages.  Full  leather,  Hmp,  with 
gold  edges.     $1.00  net ;  with  patent  thumb  index,  ^1.25  net. 

James  W.  Holland.  M.  D.. 

Professor  of  Medical    Chemistry    and    Toxicology   at  the  Jefferson    Medical    College, 

Philadelphia. 
"  I  am  struck  at  once  with  admiration  at  the   compact  size  and  attractive   exterior.     I 
can  recommend  it  to  our  students  without  reserve." 

Cragin*s  Gynecology.  New  (6th)  Edition 

Essentials  of  Gynecology.  By  Edwin  B.  Cragin,  M.  D., 
Professor  of  Obstetrics,  College  of  Physicians  and  Surgeons,  New 
York.  Crown  octavo,  215  pages,  62  illustrations.  Cloth,  ;^i.oo 
net.     In  Saunders'   Questioji-Coinpend  Series. 

The  Medical  Record,  New  York 

"A  handy  volume  and  a  distinct  improvement  of  students'  compends  in  general. 
No  author  who  was  not  himself  a  practical  gynecologist  could  have  consulted  the 
student's  needs  so  thoroughly  as  Dr.  Cragin  has  done." 

AshtOn'S    Obstetrics.  New  (6th)  Edition 

Essentials  of  Obstetrics.  By  W.  Easterly  Ashton,  M.D., 
Professor  of  Gynecology  in  the  Medico-Chirurgical  College,  Phila- 
delphia. Crown  octavo,  256  pages,  75  illustrations.  Cloth,  ;^i.oo 
net.     hi  Saiaiders'  Question- Compend  Series. 

Southern  Practitioner 

"  An  excellent  little  volume  ccntaining  correct  and  practical  knowledge.  An  admir- 
able compend,  and  the  best  condensation  we  have  seen." 

Barton  and  Wells'  Medical  Thesaurus 

A  Thesaurus  of  Medical  Words  and  Phrases.  By  Wilfred 
M.  Barton,  M.  D.,  Assistant  to  Professor  of  Materia  Medica  and 
Therapeutics,  Georgetown  University,  Washington,  D.  C. ;  and 
Walter  A.  Wells,  M.  D.,  Demonstrator  of  Laryngology,  George- 
town University,  Washington,  D.  C.  1 2mo  of  534  pages.  Flex- 
ible leather,  ;^2.50  net;  with  thumb  index,  ;^3.oo  net, 

Macfarlane*s   Gynecology  for  Nurses 

A  Reference  Hand-Book  of  Gynecology  for  Nurses.  By  Cath- 
arine Macfarlane,  M.  D.,  Gynecologist  to  the  Woman's  Hospital  of 
Philadelphia.  32mo  of  150  pages,  with  70  iUustrations.  Flexible 
leather,  $1.25  net. 

This  new  work,  uniform  in  size  and  style  with  Beck's  Reference  Hand- 
Book,  is  a  complete  treatise  on  gynecology  for  the  nurse.  The  illustrations 
are  all  original  and  are  unusually  instructive.  Nurses  will  find  this  book — 
of  a  size  to  fit  the  pocket — a  valuable  companion. 


DATE   DUE 

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1 

GAYLORO 

PRINTED  IN  U.S.A. 

